Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response |
| |
Authors: | Gardner Brooke M Walter Peter |
| |
Affiliation: | Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. |
| |
Abstract: | The unfolded protein response (UPR) detects the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and adjusts the protein-folding capacity to the needs of the cell. Under conditions of ER stress, the transmembrane protein Ire1 oligomerizes to activate its cytoplasmic kinase and ribonuclease domains. It is unclear what feature of ER stress Ire1 detects. We found that the core ER-lumenal domain (cLD) of yeast Ire1 binds to unfolded proteins in yeast cells and to peptides primarily composed of basic and hydrophobic residues in vitro. Mutation of amino acid side chains exposed in a putative peptide-binding groove of Ire1 cLD impaired peptide binding. Peptide binding caused Ire1 cLD oligomerization in vitro, suggesting that direct binding to unfolded proteins activates the UPR. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|