7A4U

Crystal structure of lid-truncated apo BiP in an oligomeric state

7A4U の概要

• エントリーDOI: 10.2210/pdb7a4u/pdb
• 関連するPDBエントリー: 6HAB
• 分子名称: Endoplasmic reticulum chaperone BiP, GLYCEROL (3 entities in total)
• 機能のキーワード: er, endoplasmic reticulum, hsp70, grp78, chaperone
• 由来する生物種: Cricetulus griseus (Chinese hamster)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58095.61

構造登録者

Perera, L.A.,Ron, D. (登録日: 2020-08-20, 公開日: 2020-12-16, 最終更新日: 2024-01-31)

主引用文献

Preissler, S.,Rato, C.,Yan, Y.,Perera, L.A.,Czako, A.,Ron, D.
Calcium depletion challenges endoplasmic reticulum proteostasis by destabilising BiP-substrate complexes.
Elife, 9:-, 2020

PubMed Abstract: The metazoan endoplasmic reticulum (ER) serves both as a hub for maturation of secreted proteins and as an intracellular calcium storage compartment, facilitating calcium-release-dependent cellular processes. ER calcium depletion robustly activates the unfolded protein response (UPR). However, it is unclear how fluctuations in ER calcium impact organellar proteostasis. Here, we report that calcium selectively affects the dynamics of the abundant metazoan ER Hsp70 chaperone BiP, by enhancing its affinity for ADP. In the calcium-replete ER, ADP rebinding to post-ATP hydrolysis BiP-substrate complexes competes with ATP binding during both spontaneous and co-chaperone-assisted nucleotide exchange, favouring substrate retention. Conversely, in the calcium-depleted ER, relative acceleration of ADP-to-ATP exchange favours substrate release. These findings explain the rapid dissociation of certain substrates from BiP observed in the calcium-depleted ER and suggest a mechanism for tuning ER quality control and coupling UPR activity to signals that mobilise ER calcium in secretory cells.

PubMed: 33295873
DOI: 10.7554/eLife.62601

実験手法

X-RAY DIFFRACTION (1.77 Å)