6uy9

Crystal structure of the STAC3 tandem SH3 domains - P269R, W284S

spinqualitylabelsall models 6uy9, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uy9 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: EDO, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease STAC3_HUMAN Native American myopathy. Function STAC3_HUMAN Publication Abstract from PubMed STAC3 is a soluble protein essential for skeletal muscle excitation-contraction (EC) coupling. Through its tandem SH3 domains, it interacts with the cytosolic II-III loop of the skeletal muscle voltage-gated calcium channel. STAC3 is the target for a mutation (W284S) that causes Native American myopathy, but multiple other sequence variants have been reported. Here, we report a crystal structure of the human STAC3 tandem SH3 domains. We analyzed the effect of five disease-associated variants, spread over both SH3 domains, on their ability to bind to the CaV1.1 II-III loop and on muscle EC coupling. In addition to W284S, we find the F295L and K329N variants to affect both binding and EC coupling. The ability of the K329N variant, located in the second SH3 domain, to affect the interaction highlights the importance of both SH3 domains in association with CaV1.1. Our results suggest that multiple STAC3 variants may cause myopathy. Multiple Sequence Variants in STAC3 Affect Interactions with CaV1.1 and Excitation-Contraction Coupling.,Rufenach B, Christy D, Flucher BE, Bui JM, Gsponer J, Campiglio M, Van Petegem F Structure. 2020 May 27. pii: S0969-2126(20)30174-X. doi:, 10.1016/j.str.2020.05.005. PMID:32492370 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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