6HAB

Crystal structure of BiP V461F (apo)

Summary for 6HAB

• Entry DOI: 10.2210/pdb6hab/pdb
• Descriptor: Endoplasmic reticulum chaperone BiP, DI(HYDROXYETHYL)ETHER (3 entities in total)
• Functional Keywords: bip, grp78, hsp70, chaperone
• Biological source: Cricetulus griseus (Chinese hamster)
• Total number of polymer chains: 1
• Total formula weight: 57698.22

Authors

Yan, Y.,Ron, D. (deposition date: 2018-08-07, release date: 2019-02-06, Last modification date: 2024-01-17)

Primary citation

Yan, Y.,Rato, C.,Rohland, L.,Preissler, S.,Ron, D.
MANF antagonizes nucleotide exchange by the endoplasmic reticulum chaperone BiP.
Nat Commun, 10:541-541, 2019

PubMed Abstract: Despite its known role as a secreted neuroprotectant, much of the mesencephalic astrocyte-derived neurotrophic factor (MANF) is retained in the endoplasmic reticulum (ER) of producer cells. There, by unknown mechanisms, MANF plays a role in protein folding homeostasis in complex with the ER-localized Hsp70 chaperone BiP. Here we report that the SAF-A/B, Acinus, and PIAS (SAP) domain of MANF selectively associates with the nucleotide binding domain (NBD) of ADP-bound BiP. In crystal structures the SAP domain engages the cleft between NBD subdomains Ia and IIa, stabilizing the ADP-bound conformation and clashing with the interdomain linker that occupies this site in ATP-bound BiP. MANF inhibits both ADP release from BiP and ATP binding to BiP, and thereby client release. Cells lacking MANF have fewer ER stress-induced BiP-containing high molecular weight complexes. These findings suggest that MANF contributes to protein folding homeostasis as a nucleotide exchange inhibitor that stabilizes certain BiP-client complexes.

PubMed: 30710085
DOI: 10.1038/s41467-019-08450-4

Experimental method

X-RAY DIFFRACTION (2.08 Å)