Bilayer tension-induced clustering of the UPR sensor IRE1

  • Author / Creator
    Hossain, Md Zobayer
  • The endoplasmic reticulum serves as a center for protein quality control, where chaperones and foldases facilitate protein folding. IRE1 is a transmembrane protein that
    transduces proteotoxic stress signals by forming clusters and activating the unfolded
    protein response (UPR). Recent research indicates that membrane thickness variation
    due to variations in membrane composition drives IRE1 cluster formation, activating
    the UPR even without proteotoxic stress. Based on the stability of the IRE1 dimer,
    we demonstrate a direct relationship between bilayer tension and UPR activation.
    The stability of the IRE1 dimer in a (50%DOPC-50%POPC) membrane at different
    applied bilayer tensions was analyzed via molecular dynamics simulations. For both
    tensed and compressed ER membranes, the potential of mean force for IRE1 dimerization predicts a higher concentration of IRE1 dimers. This study establishes a direct
    biophysical relationship between bilayer tension and UPR activation, demonstrating
    that IRE1 is a mechanosensitive membrane protein

  • Subjects / Keywords
  • Graduation date
    Fall 2023
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.