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TitleStructural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 10815, Year 2024
Publish dateDec 30, 2024
AuthorsMarc A Morizono / Kelly L McGuire / Natalie I Birouty / Mark A Herzik /
PubMed AbstractMaintenance of protein homeostasis is necessary for cell viability and depends on a complex network of chaperones and co-chaperones, including the heat-shock protein 70 (Hsp70) system. In human ...Maintenance of protein homeostasis is necessary for cell viability and depends on a complex network of chaperones and co-chaperones, including the heat-shock protein 70 (Hsp70) system. In human mitochondria, mitochondrial Hsp70 (mortalin) and the nucleotide exchange factor (GrpEL1) work synergistically to stabilize proteins, assemble protein complexes, and facilitate protein import. However, our understanding of the molecular mechanisms guiding these processes is hampered by limited structural information. To elucidate these mechanistic details, we used cryoEM to determine structures of full-length human mortalin-GrpEL1 complexes in previously unobserved states. Our structures and molecular dynamics simulations allow us to delineate specific roles for mortalin-GrpEL1 interfaces and to identify steps in GrpEL1-mediated nucleotide and substrate release by mortalin. Subsequent analyses reveal conserved mechanisms across bacteria and mammals and facilitate a complete understanding of sequential nucleotide and substrate release for the Hsp70 chaperone system.
External linksNat Commun / PubMed:39737924 / PubMed Central
MethodsEM (single particle)
Resolution2.96 - 3.38 Å
Structure data

44675

9bls

EMDB-44675, PDB-9bls:
Structure of the human mitochondrial Hsp70 (mortalin; R126W mutant) bound to nucleotide exchange factor GrpEL1 (WT)
Method: EM (single particle) / Resolution: 2.96 Å

44676

9blt

EMDB-44676, PDB-9blt:
Structure of the human mitochondrial Hsp70 (mortalin; R126W mutant) bound to nucleotide exchange factor GrpEL1 (Y173A mutant)
Method: EM (single particle) / Resolution: 3.38 Å

44677

9blu

EMDB-44677, PDB-9blu:
Structure of the human mitochondrial Hsp70 (mortalin; R126W mutant) missing SBD-a lid bound to nucleotide exchange factor GrpEL1 (Y173A mutant)
Method: EM (single particle) / Resolution: 3.38 Å

Source
  • homo sapiens (human)
KeywordsCHAPERONE / Hsp70 / nucleotide exchange factor / mitochondria / cryoEM

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