Jin Hae Kim

Daegu Gyeongbuk Institute of Science and Technology | DGIST · Department of New Biology

The structural mechanism by which Hsp70-type chaperones interact with Hsp40-type co-chaperones has been of great interest, yet still remains a matter of debate. Here, we used solution NMR spectroscopy to investigate the ATP-/ADP-dependent interactions between Escherichia coli HscA and HscB, the specialized Hsp70/Hsp40 molecular chaperones that medi...

The Escherichia coli isc operon encodes key proteins involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Whereas extensive studies of most ISC proteins have revealed their functional properties, the role of IscX (also dubbed YfhJ), a small acidic protein encoded by the last gene in the operon, has remained in question. Previous studies sho...

Escherichia coli [2Fe-2S]-ferredoxin (Fdx) is encoded by the isc operon along with other proteins involved in the 'housekeeping' mechanism of iron-sulfur cluster biogenesis. Although it has been proposed that Fdx supplies electrons to reduce sulfane sulfur (S(0)) produced by the cysteine desulfurase (IscS) to sulfide (S(2-)) as required for the ass...

The Escherichia coli protein IscU serves as the scaffold for Fe-S cluster assembly and the vehicle for Fe-S cluster transfer to acceptor proteins, such as apoferredoxin. IscU populates two conformational states in solution, a structured conformation (S) that resembles the conformation of the holoprotein IscU-[2Fe-2S] and a dynamically disordered co...

The scaffold protein for iron-sulfur cluster assembly, apo-IscU, populates two interconverting conformational states, one disordered (D) and one structured (S) as revealed by extensive NMR assignments. At pH 8 and 25 °C, approximately 70% of the protein is S, and the lifetimes of the states are 1.3 s (S) and 0.50 s (D). Zn(II) and Fe(II) each bind...

Frataxin is a 23 KDa mitochondrial iron-binding protein that is involved in biogenesis of iron-sulfur clusters. A deficiency in frataxin can lead to Friedreich's ataxia, a progressive neurodegenerative disorder. The bacterial ortholog of eukaryotic mitochondrial frataxin, CyaY, is thought to play a role in iron-sulfur cluster assembly as an iron su...

Extracellular accumulation of amyloid-beta (Abeta) peptides in the brain plays a significant role in the development of Alzheimer's disease (AD). While the co-localization and interaction of proteins and metal ions with Abeta in extracellular milieu are established, their precise pathogenic associations remain unclear. Here we report the impact of...

Disturbances in metal ion homeostasis are linked to neurodegenerative diseases associated with amyloidogenic peptides or proteins, although the precise molecular mechanisms underlying the pathological connections between metal ions and amyloid-forming species remain elusive. Here we report the discovery of how copper affects the self-assembly and a...

Aggregation and fibrillization of transthyretin (TTR) is a fatal pathogenic process that can cause cardiomyopathic and polyneuropathic diseases in humans. Although several therapeutic strategies have been designed to prevent and treat related pathological events, there is still an urgent need to develop better strategies to improve potency and wide...

Frataxin is a 23 KDa mitochondrial iron-binding protein that is involved in biogenesis of iron sulfur clusters. A deficiency in frataxin leads to Friedreich's ataxia, a progressive neurodegenerative disorder. The bacterial ortholog of eukaryotic mitochondrial frataxin, CyaY, is thought to play a role in iron sulfur cluster assembly as an iron suppl...

Glucagon is a peptide hormone which posits a significant potential as a therapeutic molecule for various human diseases. One of the major challenges hampering medicinal application of glucagon, however, is its insoluble and aggregation-prone property. Although glucagon is dissolvable, it aggregates easily and forms amyloid fibrils. To date, despite...

Monomer dissociation and subsequent misfolding of the transthyretin (TTR) is one of the most critical causative factors of TTR amyloidosis. TTR amyloidosis causes several human diseases, such as senile systemic amyloidosis and familial amyloid cardiomyopathy/polyneuropathy; therefore, it is important to understand the molecular details of the struc...

Colloidal quantum-dots (QDs) are highly attractive materials for various optoelectronic applications owing to their easy maneuverability, high functionality, wide applicability, and low cost of mass-production. QDs usually consist of two components: the inorganic nano-crystalline particle and organic ligands that passivate the surface of the inorga...

Aggregation of intrinsically disordered amyloid β (Aβ) is a hallmark of Alzheimer’s disease. Although complex aggregation mechanisms have been increasingly revealed, structural ensembles of Aβ monomers with heterogeneous and transient properties still hamper detailed experimental accesses to early events of amyloidogenesis. We herein developed a ne...

Oxygen is a key atom that maintains biomolecular structures, regulates various physiological processes, and mediates various biomolecular interactions. Oxygen-17 (17O), therefore, has been proposed as a useful probe that can provide detailed information about various physicochemical features of proteins. This is attributed to the facts that (1) 17O...

Transthyretin (TTR) is an essential transporter of a thyroid hormone and a holo-retinol binding protein, found abundantly in human plasma and cerebrospinal fluid. In addition, this protein is infamous for its amyloidogenic propensity, causing various amyloidoses in humans, such as senile systemic amyloidosis, familial amyloid polyneuropathy, and fa...

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox...

Transthyretin (TTR), previously named prealbumin is a plasma protein secreted mainly by the liver and choroid plexus (CP) that is a carrier for thyroid hormones (THs) and retinol (vitamin A). The structure of TTR, with four monomers rich in β-chains in a globular tetrameric protein, accounts for the predisposition of the protein to aggregate in fib...

New drugs are needed for glioblastoma, an aggressive brain tumor with a dismal prognosis. We recently reported that gallium maltolate (GaM) retards the growth of glioblastoma in a rat orthotopic brain tumor model by inhibiting mitochondrial function and iron-dependent ribonucleotide reductase (RR). However, GaM's mechanism of action at the mitochon...

αB-crystallin (αBC) is a member of a small heat-shock protein (sHSP) superfamily and plays a predominant role in cellular protein homeostasis network by rescuing misfolded proteins from irreversible aggregation. αBC assembles into dynamic and polydisperse high molecular weight complexes containing 12 to 48 monomers; this variable stereochemistry of...

Nano-structured silicon anodes are attractive alternatives to graphite in lithium-ion batteries; however, despite recent progress in nano-engineered composites, its use remains limited. One of the issues, particularly in silicon-dominated anodes, is the poor Coulombic efficiency of lithium–silicon processes. Previous studies have shown that repeati...

Tris(trimethylsilyl) phosphite (P(OSi(CH3)3)3) is a multifunctional electrolyte additive for scavenging HF and forming a cathode electrolyte interphase (CEI). Systematic analysis of the HF reaction pathways and redox potentials of P(OSi(CH3)3)3, OP(OSi(CH3)3)3, P(OSiF3)3, and OP(OSiF3)3, and their reaction products, using ab initio calculations all...

The critical toxic species in over 40 human diseases are misfolded proteins. Their interaction with molecular chaperones such as Hsp90, which preferentially interacts with metastable proteins, is essential for the blocking of disease progression. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the three-dimensional structure...

Mutationen im Protein Transthyretin können Transthyretin-Amyloidose hervorrufen sowie Individuen davor schützen. Wenig ist jedoch über die strukturelle Basis pathogener und klinisch schützender Transthyretin-Mutanten bekannt. Hier berichten wir über die Lösungsstruktur eines Transthyretin-Monomers, das die klinisch wichtige T119M-Mutation trägt. Di...

Mutations in the protein transthyretin can cause as well as protect individuals from transthyretin amyloidosis, an incurable fatal inherited disease. Little is known, however, about the structural basis of pathogenic and clinically protective transthyretin mutants. Here we determined the solution structure of a transthyretin monomer that carries th...

Protein misfolding and aggregation are pathological events that place a significant amount of stress on the maintenance of protein homeostasis (proteostasis). For prevention and repair of protein misfolding and aggregation, cells are equipped with robust mechanisms that mainly rely on molecular chaperones. Two classes of molecular chaperones, heat...

Proteins containing iron-sulfur (Fe-S) clusters arose early in evolution and are essential to life. Organisms have evolved machinery consisting of specialized proteins that operate together to assemble Fe-S clusters efficiently so as to minimize cellular exposure to their toxic constituents: iron and sulfide ions. To date, the best studied system i...

Proteins from the isc operon of Escherichia coli constitute the machinery used to synthesize iron-sulfur (Fe-S) clusters for delivery to recipient apo-proteins. Efficient and rapid [2Fe-2S] cluster transfer from the holo-scaffold protein IscU depends on ATP hydrolysis in the nucleotide-binding domain (NBD) of HscA, a specialized Hsp70-type molecula...

IscU, the scaffold protein for the major iron-sulfur cluster biosynthesis pathway in microorganisms and mitochondria (ISC pathway), plays important roles in the formation of [2Fe-2S] and [4Fe-4S] clusters and their delivery to acceptor apo-proteins. Our laboratory has shown that IscU populates two distinct, functionally relevant, conformational sta...

Background Iron-sulfur cluster biosynthesis involves a scaffold protein (ISCU), cysteine desulfurase (NFS1), chaperone (mtHSP70), and co-chaperone (HSC20). Results: Human mitochondrial ISCU populates structured (S) and disordered (D) conformational states. S interacts preferentially with NFS1 and mtHSP70; D interacts preferentially with HSC20. Conc...

IscU from Escherichia coli, the scaffold protein for iron-sulfur cluster biosynthesis and delivery, populates a complex energy landscape. IscU exists as two slowly interconverting species: one (S) is largely structured with all four peptidyl-prolyl bonds trans; the other (D) is partly disordered but contains an ordered domain that stabilizes two ci...

The highly conserved protein, IscU, serves as the scaffold for iron-sulfur cluster (ISC) assembly in the ISC system common to bacteria and eukaryotic mitochondria. The apo-form of IscU from Escherichia coli has been shown to populate two slowly interconverting conformational states: one structured (S) and one dynamically disordered (D). Furthermore...

PONDEROSA (Peak-picking Of Noe Data Enabled by Restriction of Shift Assignments) accepts input information consisting of a protein sequence, backbone and sidechain NMR resonance assignments, and 3D-NOESY (13C-edited and/or 15N-edited) spectra, and returns assignments of NOESY crosspeaks, distance and angle constraints, and a reliable NMR structure...

IscU is a scaffold protein that functions in iron-sulfur cluster assembly and transfer. Its critical importance has been recently underscored by the finding that a single intronic mutation in the human iscu gene is associated with a myopathy resulting from deficient succinate dehydrogenase and aconitase [Mochel, F., Knight, M. A., Tong, W. H., Hern...