8GB3

Structure of the Mycobacterium tuberculosis Hsp70 protein DnaK bound to the nucleotide exchange factor GrpE

8GB3 の概要

• エントリーDOI: 10.2210/pdb8gb3/pdb
• EMDBエントリー: 29912
• 分子名称: Chaperone protein DnaK, Protein GrpE (2 entities in total)
• 機能のキーワード: heat shock protein 70, nucleotide exchange factor, protein folding and refolding, chaperone
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 116029.79

構造登録者

Xiao, X.,Li, H. (登録日: 2023-02-24, 公開日: 2024-01-31, 最終更新日: 2024-05-01)

主引用文献

Xiao, X.,Fay, A.,Molina, P.S.,Kovach, A.,Glickman, M.S.,Li, H.
Structure of the M. tuberculosis DnaK-GrpE complex reveals how key DnaK roles are controlled.
Nat Commun, 15:660-660, 2024

PubMed Abstract: The molecular chaperone DnaK is essential for viability of Mycobacterium tuberculosis (Mtb). DnaK hydrolyzes ATP to fold substrates, and the resulting ADP is exchanged for ATP by the nucleotide exchange factor GrpE. It has been unclear how GrpE couples DnaK's nucleotide exchange with substrate release. Here we report a cryo-EM analysis of GrpE bound to an intact Mtb DnaK, revealing an asymmetric 1:2 DnaK-GrpE complex. The GrpE dimer ratchets to modulate both DnaK nucleotide-binding domain and the substrate-binding domain. We further show that the disordered GrpE N-terminus is critical for substrate release, and that the DnaK-GrpE interface is essential for protein folding activity both in vitro and in vivo. Therefore, the Mtb GrpE dimer allosterically regulates DnaK to concomitantly release ADP in the nucleotide-binding domain and substrate peptide in the substrate-binding domain.

PubMed: 38253530
DOI: 10.1038/s41467-024-44933-9

実験手法

ELECTRON MICROSCOPY (3.7 Å)