7T8B
Octameric Human Twinkle Helicase Clinical Variant W315L
Summary for 7T8B
Entry DOI | 10.2210/pdb7t8b/pdb |
EMDB information | 25743 |
Descriptor | Twinkle mtDNA helicase (1 entity in total) |
Functional Keywords | helicase, walker a, walker b, dna binding, dna binding protein |
Biological source | Homo sapiens (human) |
Total number of polymer chains | 8 |
Total formula weight | 627755.38 |
Authors | Riccio, A.A.,Bouvette, J.,Krahn, J.,Borgnia, M.J.,Copeland, W.C. (deposition date: 2021-12-16, release date: 2022-07-27, Last modification date: 2024-02-28) |
Primary citation | 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 Cited by 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: 35914129DOI: 10.1073/pnas.2207459119 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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