9BLT
Structure of the human mitochondrial Hsp70 (mortalin; R126W mutant) bound to nucleotide exchange factor GrpEL1 (Y173A mutant)
Summary for 9BLT
| Entry DOI | 10.2210/pdb9blt/pdb |
| EMDB information | 44676 |
| Descriptor | Stress-70 protein, mitochondrial, GrpE protein homolog 1, mitochondrial, Substrate peptide (3 entities in total) |
| Functional Keywords | hsp70, chaperone, nucleotide exchange factor, mitochondria, cryoem |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 101467.95 |
| Authors | Morizono, M.A.,McGuire, K.L.,Birouty, N.I.,Herzik Jr., M.A. (deposition date: 2024-05-01, release date: 2025-01-15) |
| Primary citation | Morizono, M.A.,McGuire, K.L.,Birouty, N.I.,Herzik Jr., M.A. Structural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70. Nat Commun, 15:10815-10815, 2024 Cited by PubMed Abstract: 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. PubMed: 39737924DOI: 10.1038/s41467-024-54499-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.38 Å) |
Structure validation
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