Ian A Taylor's research while affiliated with The Francis Crick Institute and other places
What is this page?
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
Publications (165)
SAMHD1 regulates cellular nucleotide homeostasis, controlling dNTP levels by catalysing their hydrolysis into 2’-deoxynucleosides and triphosphate. In differentiated CD4+ macrophage and resting T-cells SAMHD1 activity results in the inhibition of HIV-1 infection through a dNTP blockade. In cancer, SAMHD1 desensitizes cells to nucleoside-analogue ch...
RAD52 is important for the repair of DNA double-stranded breaks1,2, mitotic DNA synthesis3–5 and alternative telomere length maintenance6,7. Central to these functions, RAD52 promotes the annealing of complementary single-stranded DNA (ssDNA)8,9 and provides an alternative to BRCA2/RAD51-dependent homologous recombination repair¹⁰. Inactivation of...
The sterile alpha motif and histidine-aspartate (HD) domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several haematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in...
The sterile alpha motif and histidine-aspartate (HD) domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several haematological malignancies. Targeting SAMHD1’s ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in...
Lenacapavir, targeting the HIV-1 capsid, is the first-in-class antiretroviral drug recently approved for clinical use. The development of Lenacapavir is attributed to the remarkable progress in our understanding of the capsid protein made during the last few years. Considered little more than a component of the virus shell to be shed early during i...
Poly(ADP-ribose) polymerase (PARP) inhibitors are used in the clinic to treat BRCA -deficient breast, ovarian and prostate cancers. As their efficacy is potentiated by loss of the nucleotide salvage factor DNPH1 there is considerable interest in the development of highly specific small molecule DNPH1 inhibitors. Here, we present X-ray crystal struc...
m6A methylation provides an essential layer of regulation in organismal development, and is aberrant in a range of cancers and neuro-pathologies. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by RNA binding proteins that recognise methylated sites, the m6A readers. m6A readers include a well-characte...
Understanding how the RNA-binding domains of a protein regulator are used to recognize its RNA targets is a key problem in RNA biology, but RNA-binding domains with very low affinity do not perform well in the methods currently available to characterize protein-RNA interactions. Here, we propose to use conservative mutations that enhance the affini...
Background
SAMHD1 is a deoxynucleotide triphosphohydrolase that restricts replication of HIV-1 in differentiated leucocytes. HIV-1 is not restricted in cycling cells and it has been proposed that this is due to phosphorylation of SAMHD1 at T592 in these cells inactivating the enzymatic activity. To distinguish between theories for how SAMHD1 restri...
Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are an emerging class of small molecules that disrupt viral maturation by inducing the aberrant multimerization of IN. Here, we present cocrystal structures of HIV-1 IN with two potent ALLINIs, namely, BI-D and the drug candidate Pirmitegravir. The structures reveal atomistic details of the ALLIN...
The zinc finger antiviral protein (ZAP) inhibits viral replication by directly binding CpG dinucleotides in cytoplasmic viral RNA to inhibit protein synthesis and target the RNA for degradation. ZAP evolved in tetrapods and there are clear orthologs in reptiles, birds, and mammals. When ZAP emerged, other proteins may have evolved to become cofacto...
The zinc finger antiviral protein (ZAP) inhibits viral replication by directly binding CpG dinucleotides in cytoplasmic viral RNA to inhibit protein synthesis and target the RNA for degradation. ZAP evolved in tetrapods and there are clear orthologs in reptiles, birds and mammals. When ZAP emerged, other proteins may have evolved to become cofactor...
Solution and solid-state NMR spectroscopy are highly complementary techniques for studying structure and dynamics in very high molecular weight systems. Here we have analysed the dynamics of HIV-1 capsid (CA) assemblies in presence of the cofactors IP6 and ATPγS and the host-factor CPSF6 using a combination of solution state and cross polarisation...
A multimer of retroviral integrase (IN) synapses viral DNA ends within a stable intasome nucleoprotein complex for integration into a host cell genome. Reconstitution of the intasome from the maedi-visna virus (MVV), an ovine lentivirus, revealed a large assembly containing sixteen IN subunits¹. Herein, we report cryo-EM structures of the lentivira...
Eukaryotes are continually subjected to viral infections and, in response, have evolved a wide range of defence mechanisms. Two recent studies show how a duplicated copy of a cellular protein needed for cell growth and virus egress evolved to inhibit viruses while preserving cell viability.
A multimer of retroviral integrase (IN) synapses viral DNA ends within a stable intasome nucleoprotein complex for integration into a host cell genome. Reconstitution of the intasome from the maedi-visna virus (MVV), an ovine lentivirus, revealed a large assembly containing sixteen IN subunits. Herein, we report cryo-EM structures of the lentiviral...
The zinc finger antiviral protein (ZAP) restricts a broad range of viruses by binding CpG dinucleotides in viral RNA to target it for degradation and inhibit its translation. KHNYN was recently identified as an antiviral protein required for ZAP to inhibit retroviral replication, though little is known about its functional determinants. KHNYN conta...
Excessive replication of Saccharomyces cerevisiae Ty1 retrotransposons is regulated by Copy Number Control, a process requiring the p22/p18 protein produced from a sub-genomic transcript initiated within Ty1 GAG . In retrotransposition, Gag performs the capsid functions required for replication and re-integration. To minimize genomic damage, p22/p1...
The capsid (CA) lattice of the HIV-1 core plays a key role during infection. From the moment the core is released into the cytoplasm, it interacts with a range of cellular factors that, ultimately, direct the pre-integration complex to the integration site. For integration to occur, the CA lattice must disassemble. Early uncoating or a failure to d...
Viruses have evolved means to manipulate the host's ubiquitin-proteasome system, in order to down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp the substrate receptor DCAF1 of host Cullin4-RING ligases (CRL4), a family of modular ubiquitin ligases involved in DNA replication, DNA repair and cell cycle re...
SAMHD1 is a fundamental regulator of cellular dNTPs that catalyzes their hydrolysis into 2′-deoxynucleoside and triphosphate, restricting the replication of viruses, including HIV-1, in CD4⁺ myeloid lineage and resting T-cells. SAMHD1 mutations are associated with the autoimmune disease Aicardi-Goutières syndrome (AGS) and certain cancers. More rec...
Chl1 is a member of the XPD family of 5’-3’ DNA helicases, which perform a variety of roles in genome maintenance and transmission. They possess a variety of unique structural features, including the presence of a highly variable, partially-ordered insertion in the helicase domain 1. Chl1 has been shown to be required for chromosome segregation in...
Viruses have evolved means to manipulate the host’s ubiquitin-proteasome system, in order to down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp the substrate receptor DCAF1 of host Cullin4-RING ligases (CRL4), a family of modular ubiquitin ligases involved in DNA replication, DNA repair and cell cycle re...
Three strikes to knock cancer out
BRCA1 and BRCA2 are tumor-suppressor genes, and patients with mutations in these genes are predisposed to breast, ovarian, and other cancers. Because BRCA1 and BRCA2 mutations affect pathways involved in DNA break repair, these patients' tumors are usually vulnerable to treatments that further damage DNA repair, su...
The capsid (CA) lattice of the HIV-1 core plays a key role during infection. From the moment the core is released into the cytoplasm, it interacts with a range of cellular factors that, ultimately, direct the pre-integration complex to the integration site. For integration to occur, the CA lattice must disassemble. Early uncoating or a failure to d...
SAMHD1 regulates cellular 2′-deoxynucleoside-5′-triphosphate (dNTP) homeostasis by catalysing the hydrolysis of dNTPs into 2′-deoxynucleosides and triphosphate. In CD4⁺ myeloid lineage and resting T-cells, SAMHD1 blocks HIV-1 and other viral infections by depletion of the dNTP pool to a level that cannot support replication. SAMHD1 mutations are as...
Microtubules are cytoskeletal polymers whose function depends on their property to switch between states of growth and shrinkage. Growing microtubules are thought to be stabilized by a GTP cap at their ends. The nature of this cap, however, is still poorly understood. End Binding proteins (EBs) recruit a diverse range of regulators of microtubule f...
The tetrapod neuronal protein ARC and its Drosophila melanogaster homolog, dARC1, have important but differing roles in neuronal development. Both are thought to originate through exaptation of ancient Ty3/Gypsy retrotransposon Gag, with their novel function relying on an original capacity for self-assembly and encapsidation of nucleic acids. Here,...
The HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old. Many maintain intact open reading frames and provirus expression together with HML2 particle formation are observed in early stage human embryo development and are associated with pluripotency...
Microtubules are cytoskeletal polymers whose function depends on their property to switch between states of growth and shrinkage. Growing microtubules are thought to be stabilized by a GTP cap at their ends. The nature of this cap, however, is still poorly understood. End Binding proteins (EBs) recruit a diverse range of regulators of microtubule f...
Significance
Animals defend themselves from viral infection using innate immunity proteins that disrupt various stages of the virus life cycle. In response, viruses produce proteins that bind these host factors and compromise their activity, resulting in evolutionary conflict as immunity and virus proteins adapt to prevent and restore binding, resp...
Vertebrate protein SAMHD1 (sterile-α-motif and HD domain containing protein 1) regulates the cellular dNTP (2'-deoxynucleoside-5'-triphosphate) pool by catalysing the hydrolysis of dNTP into 2'-deoxynucleoside and triphosphate products. As an important regulator of cell proliferation and a key player in dNTP homeostasis, mutations to SAMHD1 are imp...
The tetrapod neuronal protein ARC and its D. melanogaster homologue, dARC1, have important but differing roles in neuronal development. Both are thought to originate through exaptation of ancient Ty3/Gypsy retrotransposon Gag genes, with their novel function relying on an original capacity for self-assembly and encapsidation of nucleic acids. Here,...
IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-bind...
In rice, the critical regulator of the salicylic acid signalling pathway is OsWRKY45, a transcription factor (TF) of the WRKY TF family that functions by binding to the W-box of gene promoters, but the structural basis of OsWRKY45/W-box DNA recognition is unknown. Here, we show the crystal structure of the DNA binding domain of OsWRKY45 (OsWRKY45–D...
The Cul3 adaptor Btbd6 plays crucial roles in neural development by driving the ubiquitin-dependent degradation of promyelocytic zinc finger transcription factor (Plzf). Btbd6 has conserved motifs, BTB-BACK-PHR, and by analogy with other BTB-BACK adaptors, might be expected to bind to Cul3 through the BTB-BACK domain, and to substrate through the P...
Fungal avirulence effectors, a key weapon utilized by pathogens to promote their infection, are recognized by immune receptors to boost host R gene‐mediated resistance. Many avirulence effectors share sparse sequence homology to proteins with known functions, and their molecular and biochemical functions together with the evolutionary relationship...
Magnaporthe oryzae is a model fungal plant pathogen employed for studying plant-fungi interactions. Whole genome sequencing and bioinformatics analyses revealed that this fungal pathogen has more than 12,000 protein-coding genes with 65% of the genes remaining functionally un-annotated. Here, we determine the structure of the hypothetical protein,...
Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previou...
We report that DNA damage induced by topoisomerase inhibitors, including etoposide (ETO), results in a potent block to HIV-1 infection in human monocyte-derived macrophages (MDM). SAMHD1 suppresses viral reverse transcription (RT) through depletion of cellular dNTPs but is naturally switched off by phosphorylation in a subpopulation of MDM found in...
Background
The Spumaretrovirinae (foamy viruses) and the Orthoretrovirinae (e.g. HIV) share many similarities both in genome structure and the sequences of the core viral encoded proteins, such as the aspartyl protease and reverse transcriptase. Similarity in the gag region of the genome is less obvious at the sequence level but has been illuminate...
RBM10 is an RNA-binding protein that plays an essential role in development and is frequently mutated in the context of human disease. RBM10 recognizes a diverse set of RNA motifs in introns and exons and regulates alternative splicing. However, the molecular mechanisms underlying this seemingly relaxed sequence specificity are not understood and f...
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level tha...
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level tha...
GINS is a key component of eukaryotic replicative forks and is composed of four subunits (Sld5, Psf1, Psf2, Psf3). To explain the discrepancy between structural data from crystallography and electron microscopy (EM), we show that GINS is a compact tetramer in solution as observed in crystal structures, but also forms a double-tetrameric population,...
High-resolution insights into the intasome
An essential step in the life cycle of lentiviruses such as HIV-1 is when viral DNA integrates into the host genome, establishing a permanent infection of the host cell. The viral integrase enzyme catalyzes this process and is a major drug target. During viral integration, integrase binds the ends of viral...
Background:
HIV-1 capsid influences viral uncoating and nuclear import. Some capsid is detected in the nucleus but it is unclear if it has any function. We reported that the antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration and that a capsid mutation confers resistance to C-A1, suggesting that capsid might affect post-nuclear entry steps...
The Eleventh International Foamy Virus Conference took place on 9–10 June 2016 at the Institut Pasteur, Paris, France. The meeting reviewed progress on foamy virus (FV) research, as well as related current topics in retrovirology. FVs are complex retroviruses that are widespread in several animal species. Several research topics on these viruses ar...
Helical connectivity and topology.
(A) Secondary structure elements in HIV-1 CA and PFV-Gag(300–477). The position of secondary structure elements in the HIV-1 and PFV sequences are highlighted above and below the sequences respectively. Helices and strands are represented by coils and arrows; HIV-1 CA-NTD and PFV Gag-NtDCEN (Blue), HIV-1 CA-CTD an...
Conserved PGQA and YxxLGL motifs.
(A) Primary sequence of PFV-Gag CtDCEN. The highly conserved PGQA and YxxLGL motifs are highlighted in blue and green respectively and residues at the homodimer interface (helices α5 and α6) are highlighted in red. (B) PFV-Gag CTDCEN monomer structure. The monomer is shown in surface representation with secondary s...
NMR data for PFV-Gag CtDCEN homodimer.
(A) Family of PFV-Gag CtDCEN homodimer NMR structures. The protein backbone for each of the 20 conformers in the final refinement is shown in ribbon representation. The backbone of one monomer is coloured from the N- to C-terminus in blue to red and α-helices are labelled sequentially. The other monomer is sho...
SSM superpose scores for structural alignments
(PDF)
The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information...
Quantitation of viral cores
(PDF)
Concentration dependence of PFV Gag-CtDCEN sedimentation.
C(S) distributions derived from sedimentation velocity data recorded from PFV Gag-CtDCEN at 16μM (orange), 76 μM (green) and 123 μM (blue) are shown. The proportion of fast moving 2.07 S dimer component increases with increasing concentration.
(TIF)
NMR data for PFV Gag(300–477).
(A) Family of PFV Gag(300–477) NMR structures. The protein backbone for each of the 20 conformers in the final refinement is shown in ribbon representation. The backbone is coloured from the N- to C-terminus in blue to red and α-helices are labelled sequentially. (B) Backbone 15N relaxation parameters of PFV Gag(300–4...
The eukaryotic protein Isd11 is a chaperone that binds and stabilizes the central component of the essential metabolic pathway responsible for formation of iron-sulfur clusters in mitochondria, the desulfurase Nfs1. Little is known about the exact role of Isd11. Here, we show that human Isd11 (ISD11) is a helical protein which exists in solution as...
Peptide Table Report for MS analysis.
(XLSX)
Source Data for Figure 2
Expanded View Figures PDF
Source Data for Figure 4
Review Process File
Source Data for Figure 5
TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization...
Author Summary
SAMHD1 is a restriction factor that blocks infection of certain immune cells by HIV-1. It was discovered to be an enzyme that catalyses the breakdown of dNTPs, suggesting that it inhibits HIV-1 replication by reducing cellular dNTP pools to such low levels that reverse transcriptase cannot function. However, recently, alternative mec...
The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation. We present th...
PC4, a well-known general transcription cofactor, has multiple functions in transcription and DNA repair. Residue W89, is engaged in stacking interactions with DNA in PC4, but substituted by tyrosine in some PC4 orthologous proteins. In order to understand the consequences and reveal the molecular details of this substitution we have determined the...
The hnRNP K-homology (KH) domain is a single stranded nucleic acid binding domain that mediates RNA target recognition by a large group of gene regulators. The structure of the KH fold is well characterised and some initial rules for KH-RNA recognition have been drafted. However, recent findings have shown that these rules need to be revisited and...
The MBP1 family proteins are the DNA binding subunits of MBF cell-cycle transcription factor complexes and contain an N terminal winged helix-turn-helix (wHTH) DNA binding domain (DBD). Although the DNA binding mechanism of MBP1 from Saccharomyces cerevisiae has been extensively studied, the structural framework and the DNA binding mode of other MB...
The development of deoxynucleoside triphosphate (dNTP)-based drugs requires a quantitative understanding of any inhibition,
activation, or hydrolysis by off-target cellular enzymes. SAMHD1 is a regulatory dNTP-triphosphohydrolase that inhibits HIV-1
replication in human myeloid cells. We describe here an enzyme-coupled assay for quantifying the act...
Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), a Mendelian inflammatory disease which displays remarkable clinical and biochemical overlap with congenital viral infection. SAMHD1 has also been defined as an HIV-1 restriction-factor that, through a novel triphosphohydrolase activity, inhibits early stage HIV-1 replication in myeloid der...
FAN1 is a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. It is the only eukaryotic protein with a virus-type replication-repair nuclease ("VRR-Nuc") "module" that commonly occurs as a standalone domain in many bacteria and viruses. Crystal structures of three represe...
Significance
Retroviral infection of cells can be blocked by the action of the postentry restriction factors. The Trim5α and Fv1 factors do so by targeting the capsid that surrounds the viral core. The nature of the interaction of these factors with the viral assembly is unclear. We show that these factors form antiparallel dimers that display spec...
Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection of myeloid-lineage cells as well as resting CD4(+) T cells by reducing the cellular deoxynucleoside 5'-trip...
Restriction of PFV and SFVmac by Brown Capuchin Trim5α. The table shows the results of restriction assays were mutations have been introduced into a Human-Brown Capuchin Trim5α hybrid comprising the RING, B-box and coiled coil domains of human Trim5α and the B30.2 domain from Brown Capuchin Trim5α. Values are the ratio of the percentage of infected...
Restriction of chimeric PFV and SFVmac. The table shows the degree of restriction of PFV and SFVmac along with chimeric PGS-4, SPG-4, PSG-5 and SPG-5. Values are the ratio of the percentage of infected restriction factor-positive cells to the percentage of infected cells not expressing the restriction. A lower than 0.3 was taken to represent restri...
Structural alignment of free and bound PFV-Gag-NtD. (A) Structurally aligned free and bound PFV-Gag-NtD are shown in cartoon representation and the bound Env peptides as cylinders. Regions that align well are shaded grey in both structures. Loop regions were significant deviations occur, the α1-β1 and β3–β4 loops, are coloured blue (free) and green...
Sedimentation velocity analysis of Gag-Env interface mutants. C(S) functions that best fit sedimentation velocity profiles for Env binding experiments from (A) V18S, (B) L21S, (C) L21N, (D) V14S/V18SS, (E) V18S/L21S and (F) V14S/V18S/L21S mutants. The C(S) function from 75 µM Gag NTD (black) and from 75 µM equimolar mixtures of Gag NtDs with Env1–2...
The Spumaretrovirinae, or foamyviruses (FVs) are complex retroviruses that infect many species of monkey and ape. Although FV infection is apparently benign, trans-species zoonosis is commonplace and has resulted in the isolation of the Prototypic Foamy Virus (PFV) from human sources and the potential for germ-line transmission. Despite little sequ...
Infectivity of particles used in TRIM5alpha and Fv1 saturation assays (Figure4). (A) LacZ-encoding N-MLV tester viruses, with or without p12 mutations, or B-MLV were synthesized in 293T cells and used in TRIM5alpha and Fv1b abrogation assays (Figure
4A and
4B). Equal RT-units of VLPs were used to challenge D17, TE671 and B3T3 cells and infectivity...
Quantification of viral cDNA levels in D17 cells. Wild type and mutant N-MLV VLPs were produced in 293T cells by transient transfection and equal RT-units of VLPs were used to challenge D17 cells. Total DNA was isolated at various times post infection as indicated, and the relative amounts of second strand extension were measured using qPCR. Result...
Activity of p12 mutants in a panel of cell lines. Wild type Mo-MLV or p12 mutants 5, 6, 8 and 13 VLPs were produced in 293T cells by transient transfection and virus production was quantified by RT-ELISA. Equivalent RT-units of VLPs were used to challenge a panel of cell lines from different species and productive infection was measured after 48 ho...
The Moloney murine leukaemia virus (Mo-MLV) gag gene encodes three main structural proteins, matrix, capsid and nucleocapsid and a protein called p12. In addition to its role during the late stages of infection, p12 has an essential, but undefined, function during early post-entry events. As these stages of retroviral infection remain poorly unders...
Citations
... Cotransfection with both siRNAs showed a more pronounced effect than with each siRNA individually. This is consistent with a model whereby IMP1 binding to specific targets can be enhanced by m6A methylation, as we proposed based on the structure and biophysical characterisation of the IMP1 KH4-m6A interaction 24 . Importantly, overexpression of IMP1 leads to increased expression, which is abrogated when m6A is reduced through METTL3 KD (Fig. 6c). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/11431281138034303-1680713530161_Q64/Giancarlo-Abis.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/511822412824576-1499039380359_Q64/Pierre-Klein.jpg)
... We here focused on solution NMR spectroscopy as a valuable tool to en-detail correlate chemical shift information with binding modes. CSP patterns, i.e. trajectories, magnitudes and exchange regimes, are unambiguous indicators of a protein domain's preference for nucleic acid as recently shown in similar studies by us 37,67 and others 87,88 . As such, CSPs can be used to compare DNA and RNA-binding by Arid5a and consequently the approach is transferable to other nucleic acid-binding domains of interest. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/901224966672385-1591880184395_Q64/Belen-Chaves-Arquero.jpg)
... Removal of regulation through Thr592 dephosphorylation or mutation has been proposed to allow SAMHD1 to inhibit HIV-1 in cycling cells 56 . Although more recently this activity in cycling cells has been shown to require attenuation of the HIV-1 reverse transcriptase 61 . ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/540251061841921-1505817298896_Q64/Sarah-Caswell-2.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/360134967611393-1462874275754_Q64/Kate-Bishop-2.jpg)
... Recent cutting-edge HIV-1 drugs to reach clinical trials do not target enzymatic active sites. Instead, allosteric inhibitors of integrase (ALLINIs) target an allosteric surface on the HIV-1 intasome, inducing IN multimerization and aberrant virion formation, whereas LEN tightly binds adjacent p24 monomers to prevent capsid disassembly [34,52,53]. Structures of deltaretroviral intasomes are now available, and an allosteric surface corresponding to ALLINIs interface may exist but is yet to be determined. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/327088239333377-1454995321893_Q64/Tung-Dinh-2.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/806007596937217-1569178594077_Q64/Peter-Cherepanov.jpg)
... In the mature core, IP6 binds in the central channel of the CA-NTD hexamer(Mallery et al., 2018). Crystal and cryoEM structures show that two IP6 molecules are bound at the 6-fold axis of the hexamer(Dick et al., 2018a; Dick et al., 2018b;Nicastro et al., 2022) that sit above and below a basic ring formed by the sidechains of Arg18 and make a network of electrostatic interactions with further contributions from a second ring of basic Lys25 sidechains (Figure 2B). ...
Reference: The capsid revolution
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1142553554485248-1649417403255_Q64/Massimo-Lucci.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/644598267379715-1530695611528_Q64/Alain-Oregioni.jpg)
... UCSF Chimera 28 , PyMOL, Coot 29 and Phenix 30 were used for model building, refinement and validation. Previous crystal structures (PDB: 2B4J) 14 , and cryoEM structures (5U1C, 6VDK, 6PUT and 7U32) 4,5,9,31 facilitated the model building. is consistent with hexadecamer intasomes and only represents about 3% of the total picked particles. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/397911503458305-1471880903557_Q64/Allison-Ballandras-Colas.jpg)
... Inside the host, viruses control cell machinery and epigenetic processes for replication, cause instability by disrupting DNA structure and transcription, and inhibit the host's immune response pathways. [1][2][3][4] Table 1 depicts Baltimore's viruses' classification into seven groups which are based on the mRNA production mechanism, whether single-stranded (ss) RNA or double-stranded (ds) DNA and reverse transcriptase (RT) machinery. [5][6] ...
... This mechanism relies on the expression of an N-truncated variant of the Ty1 capsid/nucleocapsid Gag protein (p22) from two downstream alternative start codons Saha et al., 2015). The expression of p22 scales up with the CN of Ty1 elements that encode it (Tucker et al., 2015), which gradually interferes with the assembly of the viral-like particles essential for Ty1 replication (Cottee et al., 2021;Saha et al., 2015). Thus, CNC yields a steep negative relationship between the retrotransposition rate measured with a tester element and the number of Ty1 copies in the genome (Garfinkel et al., 2003;Tucker et al., 2015). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1124608497463298-1645138968123_Q64/Matthew-Cottee.jpg)
... HIV-1 DNA integration step establishes a provirus in the host genome that serves as a permanent genetic element for the production of progeny virions [24]. However, these early steps of HIV-1 infection are critically dependent on binding of host factors/proteins to the viral capsid [25,26]. For instance, trafficking of the viral capsid to the NPC is facilitated by the kinesin adapter protein FEZ1 [27,28]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1071539424333824-1632486315731_Q64/Anabel-Guedan.jpg)
... We evaluated AlphaLink on challenging heteromeric CASP15 (Critical Assessment of Structure Prediction 9 ) and antibody-antigen targets with simulated crosslinks. Moreover, we validated AlphaLink on in-cell crosslinking MS data 5 from Bacillus subtilis that used a different crosslinker, and a virally modified Cullin4-RING ubiquitin ligase (CRL4) complex 10,11 . We focused the evaluation on heteromeric assemblies, since homomers pose a different challenge. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/281162896429058-1444045867080_Q64/Sofia-Banchenko.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/490579663560705-1493974714288_Q64/Ferdinand-Krupp.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1082773737615364-1635164784744_Q64/Joerg-Buerger.jpg)
