TY  - JOUR
A1  - Väth, Kristina
A1  - Mattes, Carsten
A1  - Reinhard, John
A1  - Covino, Roberto
A1  - Stumpf, Heike
A1  - Hummer, Gerhard
A1  - Ernst, Robert
T1  - Cysteine cross-linking in native membranes establishes the transmembrane architecture of Ire1
T2  - The journal of cell biology
N2  - The 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 cross-linking 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.
KW  - Biochemistry
KW  - Biophysics
KW  - Membrane and lipid biology
KW  - Protein homeostasis
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/71181
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-711818
SN  - 1540-8140
N1  - All data discussed in the paper are included in this published article and in the online supplemental material. Additional materials including qPCR data, microscopy data, and the immunoblots contributing to the bar diagrams in Fig. 3 F; Fig. 5, B and D; and Fig. 6 F have been deposited to Mendeley Data (DOI:10.17632/s52vt8spmc.1).
N1  - This work was supported by the Deutsche Forschungsgemeinschaft (SFB807 “Transport and Communication across Biological Membranes” to R. Ernst and G. Hummer; SFB894 “Ca2+-Signals: Molecular Mechanisms and Integrative Functions” to R. Ernst).

This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 866011).
VL  - 220
IS  - 8, art. e202011078
SP  - 1
EP  - S8
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -