6JTG

Structural insights into G domain dimerization and pathogenic mutations of OPA1

6JTG の概要

• エントリーDOI: 10.2210/pdb6jtg/pdb
• 分子名称: Dynamin-like 120 kDa protein, mitochondrial,OPA1 protein, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: mitochondria, fusion, opa1, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39514.91

構造登録者

Yan, L.,Hu, J. (登録日: 2019-04-11, 公開日: 2020-04-22, 最終更新日: 2024-03-27)

主引用文献

Yu, C.,Zhao, J.,Yan, L.,Qi, Y.,Guo, X.,Lou, Z.,Hu, J.,Rao, Z.
Structural insights into G domain dimerization and pathogenic mutation of OPA1.
J.Cell Biol., 219:-, 2020

PubMed Abstract: The fusion of mammalian inner mitochondrial membranes (IMMs) is mediated by dynamin-like GTPase OPA1. Mutations in human OPA1 cause optic atrophy, but the molecular basis for membrane fusion and pathogenesis is not clear. Here, we determined the crystal structure of the minimal GTPase domain (MGD) of human OPA1. A three-helix bundle (HB) domain including two helices extending from the GTPase (G) domain and the last helix of OPA1 tightly associates with the G domain. In the presence of GDP and BeF3-, OPA1-MGD forms a dimer, the interface of which is critical for the maintenance of mitochondrial morphology. The catalytic core of OPA1 possesses unique features that are not present in other dynamin-like proteins. Biochemical experiments revealed that OPA1-MGD forms nucleotide-dependent dimers, which is important for membrane-stimulated GTP hydrolysis, and an N-terminal extension mediates nucleotide-independent dimerization that facilitates efficient membrane association. Our results suggest a multifaceted assembly of OPA1 and explain the effect of most OPA1 mutations on optic atrophy.

PubMed: 32379273
DOI: 10.1083/jcb.201907098

実験手法

X-RAY DIFFRACTION (2.4 Å)