TY  - INPR
A1  - Väth, Kristina
A1  - Mattes, Carsten
A1  - Reinhard, John
A1  - Covino, Roberto
A1  - Stumpf, Heike
A1  - Hummer, Gerhard
A1  - Ernst, Robert
T1  - Cysteine crosslinking in native membranes establishes the transmembrane architecture of Ire1
T2  - bioRxiv
N2  - Abstract
The endoplasmic reticulum (ER) is a key organelle of membrane biogenesis and crucial for the folding of both membrane and secretory proteins. Sensors of the unfolded protein response (UPR) monitor the unfolded protein load in the ER and convey effector functions for maintaining ER homeostasis. Aberrant compositions of the ER membrane, referred to as lipid bilayer stress, are equally potent activators of the UPR. How the distinct signals from lipid bilayer stress and unfolded proteins are processed by the conserved UPR transducer Ire1 remains unknown. Here, we have generated a functional, cysteine-less variant of Ire1 and performed systematic cysteine crosslinking experiments in native membranes to establish its transmembrane architecture in signaling-active clusters. We show that the transmembrane helices of two neighboring Ire1 molecules adopt an X-shaped configuration independent of the primary cause for ER stress. This suggests that different forms of stress converge in a common, signaling-active transmembrane architecture of Ire1.

Summary 
The endoplasmic reticulum (ER) is a hotspot of lipid biosynthesis and crucial for the folding of membrane and secretory proteins. The unfolded protein response (UPR) controls the size and folding capacity of the ER. The conserved UPR transducer Ire1 senses both unfolded proteins and aberrant lipid compositions to mount adaptive responses. Using a biochemical assay to study Ire1 in signaling-active clusters, Väth et al. provide evidence that the neighboring transmembrane helices of clustered Ire1 form an ‘X’ irrespectively of the primary cause of ER stress. Hence, different forms of ER stress converge in a common, signaling-active transmembrane architecture of Ire1.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72371
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-723711
N1  - Preprint, später in Journal of Cell Biology doi: 10.1083/jcb.202011078
IS  - 772772
ER  -