6ZYI

Crystal structure of HSP70 ATPase domain in complex with ADP and calcium

Summary for 6ZYI

• Entry DOI: 10.2210/pdb6zyi/pdb
• Descriptor: Heat shock 70kDa protein 1A variant, ADENOSINE-5'-DIPHOSPHATE, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: hsp70, nbd, atpase domain, chaperone, adp
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 42189.49

Authors

Yan, Y.,Preissler, S.,Ron, D. (deposition date: 2020-08-01, release date: 2020-12-16, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.52 Å)