6HA7

Crystal structure of the BiP NBD and MANF complex

6HA7 の概要

• エントリーDOI: 10.2210/pdb6ha7/pdb
• 分子名称: Endoplasmic reticulum chaperone BiP, Mesencephalic astrocyte-derived neurotrophic factor, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: manf, bip, nbd, ndi, armet, hsp70, chaperone
• 由来する生物種: Cricetulus griseus (Chinese hamster); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 121862.70

構造登録者

Yan, Y.,Ron, D. (登録日: 2018-08-07, 公開日: 2019-02-06, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.49 Å)