+Search query
-Structure paper
Title | Structure of the M. tuberculosis DnaK-GrpE complex reveals how key DnaK roles are controlled. |
---|---|
Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 660, Year 2024 |
Publish date | Jan 22, 2024 |
Authors | Xiansha Xiao / Allison Fay / Pablo Santos Molina / Amanda Kovach / Michael S Glickman / Huilin Li / |
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 ...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. |
External links | Nat Commun / PubMed:38253530 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.7 - 5.8 Å |
Structure data | EMDB-29912: Cryo-EM 3D map of the Mycobacterium tuberculosis Hsp70 protein DnaK bound to the nucleotide exchange factor GrpE EMDB-29913: Cryo-EM 3D map of the Mycobacterium tuberculosis Hsp70 protein DnaK bound to the nucleotide exchange factor GrpE EMDB-29914: Cryo-EM 3D focused map of the Mycobacterium tuberculosis Hsp70 protein DnaK SBD domain |
Source |
|
Keywords | CHAPERONE / heat shock protein 70 / nucleotide exchange factor / protein folding and refolding |