9BLU

Structure of the human mitochondrial Hsp70 (mortalin; R126W mutant) missing SBD-a lid bound to nucleotide exchange factor GrpEL1 (Y173A mutant)

9BLU の概要

• エントリーDOI: 10.2210/pdb9blu/pdb
• EMDBエントリー: 44677
• 分子名称: Stress-70 protein, mitochondrial, GrpE protein homolog 1, mitochondrial (2 entities in total)
• 機能のキーワード: hsp70, chaperone, nucleotide exchange factor, mitochondria, cryoem
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 91411.53

構造登録者

Morizono, M.A.,McGuire, K.L.,Birouty, N.I.,Herzik Jr., M.A. (登録日: 2024-05-01, 公開日: 2025-01-15)

主引用文献

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

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: 39737924
DOI: 10.1038/s41467-024-54499-1

実験手法

ELECTRON MICROSCOPY (3.38 Å)