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@article{Carrara:2015:10.15252/embj.201489183,
author = {Carrara, M and Prischi, F and Nowak, P and Ali, M},
doi = {10.15252/embj.201489183},
journal = {EMBO Journal},
pages = {1589--1600},
title = {Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling},
url = {http://dx.doi.org/10.15252/embj.201489183},
volume = {34},
year = {2015}
}

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TY  - JOUR
AB  - Stress caused by accumulation of misfolded proteins within the endoplasmic reticulum (ER) elicits a cellular unfolded protein response (UPR) aimed at maintaining proteinfolding capacity. PERK, a key upstream component, recognizes ER stress via its luminal sensor/transducer domain, but the molecular events that lead to UPR activation remain unclear. Here, we describe the crystal structures of mammalian PERK luminal domains captured in dimeric state as well as in a novel tetrameric state. Small angle Xray scattering analysis (SAXS) supports the existence of both crystal structures also in solution. The salient feature of the tetramer interface, a helix swapped between dimers, implies transient association. Moreover, interface mutations that disrupt tetramer formation in vitro reduce phosphorylation of PERK and its target eIF2α in cells. These results suggest that transient conversion from dimeric to tetrameric state may be a key regulatory step in UPR activation.
AU  - Carrara,M
AU  - Prischi,F
AU  - Nowak,P
AU  - Ali,M
DO  - 10.15252/embj.201489183
EP  - 1600
PY  - 2015///
SN  - 0261-4189
SP  - 1589
TI  - Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling
T2  - EMBO Journal
UR  - http://dx.doi.org/10.15252/embj.201489183
UR  - https://www.embopress.org/doi/full/10.15252/embj.201489183
UR  - http://hdl.handle.net/10044/1/23551
VL  - 34
ER  -

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