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| | ==Crystal structure of human STAC2 Tandem SH3 Domains Q347I (296-411)== | | ==Crystal structure of human STAC2 Tandem SH3 Domains Q347I (296-411)== |
| - | <StructureSection load='6b28' size='340' side='right' caption='[[6b28]], [[Resolution|resolution]] 2.55Å' scene=''> | + | <StructureSection load='6b28' size='340' side='right'caption='[[6b28]], [[Resolution|resolution]] 2.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6b28]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B28 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b28]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B28 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STAC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b28 OCA], [http://pdbe.org/6b28 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b28 RCSB], [http://www.ebi.ac.uk/pdbsum/6b28 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b28 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6b28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b28 OCA], [https://pdbe.org/6b28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b28 RCSB], [https://www.ebi.ac.uk/pdbsum/6b28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b28 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/STAC2_HUMAN STAC2_HUMAN] |
| - | Excitation-contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (CaV1.1) 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-A resolution. These form a rigid interaction through a conserved interdomain interface. We identify the linker connecting transmembrane repeats II and III in two different CaV 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 CaV1.2.
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| - | Structural insights into binding of STAC proteins to voltage-gated calcium channels.,Wong King Yuen SM, Campiglio M, Tung CC, Flucher BE, Van Petegem F Proc Natl Acad Sci U S A. 2017 Oct 23. pii: 201708852. doi:, 10.1073/pnas.1708852114. PMID:29078335<ref>PMID:29078335</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6b28" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Petegem, F Van]] | + | [[Category: Large Structures]] |
| - | [[Category: Tung, C C]] | + | [[Category: Tung CC]] |
| - | [[Category: Yuen, S M.Wong King]] | + | [[Category: Van Petegem F]] |
| - | [[Category: Excitation-contraction coupling]] | + | [[Category: Wong King Yuen SM]] |
| - | [[Category: Ion channel adaptor protein]]
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| - | [[Category: Protein binding]]
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