7t8b | pdb_00007t8b

Octameric Human Twinkle Helicase Clinical Variant W315L

spinqualitylabelsall models 7t8b, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7t8b is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Activity: DNA helicase, with EC number 3.6.4.12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PEO1_HUMAN] Mitochondrial DNA depletion syndrome, hepatocerebrorenal form;Infantile-onset spinocerebellar ataxia;Perrault syndrome;Autosomal dominant progressive external ophthalmoplegia;Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Function [PEO1_HUMAN] Mitochondrial helicase involved in mtDNA replication and repair (PubMed:12975372, PubMed:15167897, PubMed:17324440, PubMed:18039713, PubMed:18971204, PubMed:25824949, PubMed:26887820, PubMed:27226550). Might have a role in mtDNA repair (PubMed:27226550). Has DNA strand separation activity needed to form a processive replication fork for leading strand synthesis which is catalyzed by the formation of a replisome complex with POLG and mtSDB (PubMed:12975372, PubMed:15167897, PubMed:18039713, PubMed:22383523, PubMed:26887820, PubMed:27226550). Preferentially unwinds DNA substrates with pre-existing 5'-and 3'- single-stranded tails but is also active on a 5'- flap substrate (PubMed:12975372, PubMed:15167897, PubMed:18039713, PubMed:22383523, PubMed:26887820, PubMed:27226550). Can dissociate the invading strand of immobile or mobile D-loop DNA structures irrespective of the single strand polarity of the third strand (PubMed:27226550). In addition to its DNA strand separation activity, also has DNA strand annealing, DNA strand-exchange and DNA branch migration activities (PubMed:22383523, PubMed:26887820, PubMed:27226550). Lack DNA unwinding and ATP hydrolysis activities (PubMed:18039713). Does not bind single-stranded or double-stranded DNA (PubMed:18039713). Publication Abstract from PubMed 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. Structural insight and characterization of human Twinkle helicase in mitochondrial disease.,Riccio AA, Bouvette J, Perera L, Longley MJ, Krahn JM, Williams JG, Dutcher R, Borgnia MJ, Copeland WC Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2207459119. doi:, 10.1073/pnas.2207459119. Epub 2022 Aug 1. PMID:35914129 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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