7T8B

Octameric Human Twinkle Helicase Clinical Variant W315L

7T8B の概要

• エントリーDOI: 10.2210/pdb7t8b/pdb
• EMDBエントリー: 25743
• 分子名称: Twinkle mtDNA helicase (1 entity in total)
• 機能のキーワード: helicase, walker a, walker b, dna binding, dna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 627755.38

構造登録者

Riccio, A.A.,Bouvette, J.,Krahn, J.,Borgnia, M.J.,Copeland, W.C. (登録日: 2021-12-16, 公開日: 2022-07-27, 最終更新日: 2025-06-04)

主引用文献

Riccio, A.A.,Bouvette, J.,Perera, L.,Longley, M.J.,Krahn, J.M.,Williams, J.G.,Dutcher, R.,Borgnia, M.J.,Copeland, W.C.
Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
Proc.Natl.Acad.Sci.USA, 119:e2207459119-e2207459119, 2022

PubMed Abstract: Twinkle is the mammalian helicase vital for replication and integrity of mitochondrial DNA. Over 90 Twinkle helicase disease variants have been linked to progressive external ophthalmoplegia and ataxia neuropathies among other mitochondrial diseases. Despite the biological and clinical importance, Twinkle represents the only remaining component of the human minimal mitochondrial replisome that has yet to be structurally characterized. Here, we present 3-dimensional structures of human Twinkle W315L. Employing cryo-electron microscopy (cryo-EM), we characterize the oligomeric assemblies of human full-length Twinkle W315L, define its multimeric interface, and map clinical variants associated with Twinkle in inherited mitochondrial disease. Cryo-EM, crosslinking-mass spectrometry, and molecular dynamics simulations provide insight into the dynamic movement and molecular consequences of the W315L clinical variant. Collectively, this ensemble of structures outlines a framework for studying Twinkle function in mitochondrial DNA replication and associated disease states.

PubMed: 35914129
DOI: 10.1073/pnas.2207459119

実験手法

ELECTRON MICROSCOPY (3.8 Å)