Shangxiang Ye

Pharmaron · biochemistry and biophysics

The clinically used androgen receptor (AR) antagonists for the treatment of prostate cancer (PCa) are all targeting the AR ligand binding pocket (LBP), resulting in various drug-resistant problems. Therefore, a new strategy to combat PCa is urgently needed. Enlightened by the gain-of-function mutations of androgen insensitivity syndrome, we discove...

Mitophagy is a selective autophagic process that removes damaged mitochondria. PINK1-Parkin axis is primarily responsible for initiating mitophagy via feedforward mechanism, in which PINK1 phosphorylates ubiquitin and Parkin, and Parkin gains E3 ligase activity at the mitochondrial outer membrane. However, the phosphatase of pParkin is unknown, and...

Chemical crosslinking coupled with mass spectrometry (CXMS) has been increasingly used in structural biology. CXMS distance restraints are usually applied to Cα or Cβ atoms of the crosslinked residues, with upper bounds typically over 20 Å. The incorporation of loose CXMS restraints only marginally improves the resolution of the calculated structur...

Chemical crosslinking mass spectrometry (XLMS) is an emerging technique in structural biology. Providing the crosslinked peptides are identified by mass spectrometry with high confidence, a distance restraint can be applied between the two reactive protein residues, with the upper bound corresponding to the maximal span of the crosslinker. However,...

A signaling protein can be phosphorylated at multiple sites to gain new function. Ubiquitin (Ub), an important signaling protein in cells, can be phosphorylated by kinase PINK1 at residue S65, and the resulting pS65 Ub was shown to adopt two alternative conformations. Here we report that PINK1 can also phosphorylate Ub at residue T66. Though T66 ph...