5XIR

Solution structure for human HSP70 substrate binding domain L542Y mutant

5XIR の概要

• エントリーDOI: 10.2210/pdb5xir/pdb
• 関連するPDBエントリー: 5XI9
• NMR情報: BMRB: 36078
• 分子名称: Heat shock 70 kDa protein 1A (1 entity in total)
• 機能のキーワード: heat shock protein 70 kda, apo state, chaperone
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P0DMV8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20373.90

構造登録者

Hoshikawa, M.,Tochio, N.,Tate, S. (登録日: 2017-04-27, 公開日: 2018-05-16, 最終更新日: 2024-05-15)

主引用文献

Umehara, K.,Hoshikawa, M.,Tochio, N.,Tate, S.I.
Substrate Binding Switches the Conformation at the Lynchpin Site in the Substrate-Binding Domain of Human Hsp70 to Enable Allosteric Interdomain Communication.
Molecules, 23:-, 2018

PubMed Abstract: The stress-induced 70 kDa heat shock protein (Hsp70) functions as a molecular chaperone to maintain protein homeostasis. Hsp70 contains an N-terminal ATPase domain (NBD) and a C-terminal substrate-binding domain (SBD). The SBD is divided into the β subdomain containing the substrate-binding site (βSBD) and the α-helical subdomain (αLid) that covers the βSBD. In this report, the solution structures of two different forms of the SBD from human Hsp70 were solved. One structure shows the αLid bound to the substrate-binding site intramolecularly, whereas this intramolecular binding mode is absent in the other structure solved. Structural comparison of the two SBDs from Hsp70 revealed that client-peptide binding rearranges residues at the interdomain contact site, which impairs interdomain contact between the SBD and the NBD. Peptide binding also disrupted the inter-subdomain interaction connecting the αLid to the βSBD, which allows the binding of the αLid to the NBD. The results provide a mechanism for interdomain communication upon substrate binding from the SBD to the NBD via the lynchpin site in the βSBD of human Hsp70. In comparison to the bacterial ortholog, DnaK, some remarkable differences in the allosteric signal propagation among residues within the Hsp70 SBD exist.

PubMed: 29495458
DOI: 10.3390/molecules23030528

実験手法

SOLUTION NMR