8GB3

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

Summary for 8GB3

• Entry DOI: 10.2210/pdb8gb3/pdb
• EMDB information: 29912
• Descriptor: Chaperone protein DnaK, Protein GrpE (2 entities in total)
• Functional Keywords: heat shock protein 70, nucleotide exchange factor, protein folding and refolding, chaperone
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 3
• Total formula weight: 116029.79

Authors

Xiao, X.,Li, H. (deposition date: 2023-02-24, release date: 2024-01-31, Last modification date: 2024-05-01)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.7 Å)