6B29
Crystal structure of the second SH3 domain of STAC3 (309-364)
Summary for 6B29
| Entry DOI | 10.2210/pdb6b29/pdb |
| Descriptor | SH3 and cysteine-rich domain-containing protein 3 (2 entities in total) |
| Functional Keywords | excitation-contraction coupling, ion channel adaptor protein, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 26530.25 |
| Authors | Wong King Yuen, S.M.,Van Petegem, F. (deposition date: 2017-09-19, release date: 2017-10-25, Last modification date: 2024-03-13) |
| Primary citation | Wong King Yuen, S.M.,Campiglio, M.,Tung, C.C.,Flucher, B.E.,Van Petegem, F. Structural insights into binding of STAC proteins to voltage-gated calcium channels. Proc. Natl. Acad. Sci. U.S.A., 114:E9520-E9528, 2017 Cited by PubMed Abstract: Excitation-contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (Ca1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface. We identify the linker connecting transmembrane repeats II and III in two different Ca isoforms as a binding site for the SH3 domains and report a crystal structure of the complex with the STAC2 isoform. The interaction site includes the location for a disease variant in STAC3 that has been linked to Native American myopathy (NAM). Introducing the mutation does not cause misfolding of the SH3 domains, but abolishes the interaction. Disruption of the interaction via mutations in the II-III loop perturbs skeletal muscle EC coupling, but preserves the ability of STAC3 to slow down inactivation of Ca1.2. PubMed: 29078335DOI: 10.1073/pnas.1708852114 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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