Structural highlights
Function
GRP75_HUMAN Implicated in the control of cell proliferation and cellular aging. May also act as a chaperone.
Publication Abstract from PubMed
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.
Structural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70.,Morizono MA, McGuire KL, Birouty NI, Herzik MA Jr Nat Commun. 2024 Dec 30;15(1):10815. doi: 10.1038/s41467-024-54499-1. PMID:39737924[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Morizono MA, McGuire KL, Birouty NI, Herzik MA Jr. Structural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70. Nat Commun. 2024 Dec 30;15(1):10815. PMID:39737924 doi:10.1038/s41467-024-54499-1
