6UY7
Crystal structure of the STAC3 tandem SH3 domains - P269R
Summary for 6UY7
| Entry DOI | 10.2210/pdb6uy7/pdb |
| Descriptor | SH3 and cysteine-rich domain-containing protein 3, 1,2-ETHANEDIOL (3 entities in total) |
| Functional Keywords | protein binding domain, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14041.96 |
| Authors | Rufenach, B.,Van Petegem, F. (deposition date: 2019-11-12, release date: 2020-06-17, Last modification date: 2023-10-11) |
| Primary citation | Rufenach, B.,Christy, D.,Flucher, B.E.,Bui, J.M.,Gsponer, J.,Campiglio, M.,Van Petegem, F. Multiple Sequence Variants in STAC3 Affect Interactions with CaV1.1 and Excitation-Contraction Coupling. Structure, 28:922-, 2020 Cited by PubMed Abstract: 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 Ca1.1 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 Ca1.1. Our results suggest that multiple STAC3 variants may cause myopathy. PubMed: 32492370DOI: 10.1016/j.str.2020.05.005 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.105 Å) |
Structure validation
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