7rxe
From Proteopedia
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==Crystal structure of junctophilin-2== | ==Crystal structure of junctophilin-2== | ||
| - | <StructureSection load='7rxe' size='340' side='right'caption='[[7rxe]]' scene=''> | + | <StructureSection load='7rxe' size='340' side='right'caption='[[7rxe]], [[Resolution|resolution]] 2.35Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RXE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7rxe]] 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=7RXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RXE FirstGlance]. <br> |
| - | </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=7rxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rxe OCA], [https://pdbe.org/7rxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rxe RCSB], [https://www.ebi.ac.uk/pdbsum/7rxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rxe ProSAT]</span></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]] 2.35Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></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=7rxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rxe OCA], [https://pdbe.org/7rxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rxe RCSB], [https://www.ebi.ac.uk/pdbsum/7rxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rxe ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/JPH2_HUMAN JPH2_HUMAN] NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/JPH2_HUMAN JPH2_HUMAN] Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes (PubMed:20095964). Provides a structural foundation for functional cross-talk between the cell surface and intracellular Ca(2+) release channels by maintaining the 12-15 nm gap between the sarcolemma and the sarcoplasmic reticulum membranes in the cardiac dyads (By similarity). Necessary for proper intracellular Ca(2+) signaling in cardiac myocytes via its involvement in ryanodine receptor-mediated calcium ion release (By similarity). Contributes to the construction of skeletal muscle triad junctions (By similarity).[UniProtKB:Q9ET78]<ref>PMID:20095964</ref> Transcription repressor required to safeguard against the deleterious effects of cardiac stress. Generated following cleavage of the Junctophilin-2 chain by calpain in response to cardiac stress in cardiomyocytes. Following cleavage and release from the membrane, translocates to the nucleus, binds DNA and represses expression of genes implicated in cell growth and differentiation, hypertrophy, inflammation and fibrosis. Modifies the transcription profile and thereby attenuates pathological remodeling in response to cardiac stress. Probably acts by competing with MEF2 transcription factors and TATA-binding proteins.[UniProtKB:Q9ET78] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | SignificanceIon channels have evolved the ability to communicate with one another, either through protein-protein interactions, or indirectly via intermediate diffusible messenger molecules. In special cases, the channels are part of different membranes. In muscle tissue, the T-tubule membrane is in proximity to the sarcoplasmic reticulum, allowing communication between L-type calcium channels and ryanodine receptors. This process is critical for excitation-contraction coupling and requires auxiliary proteins like junctophilin (JPH). JPHs are targets for disease-associated mutations, most notably hypertrophic cardiomyopathy mutations in the JPH2 isoform. Here we provide high-resolution snapshots of JPH, both alone and in complex with a calcium channel peptide, and show how this interaction is targeted by cardiomyopathy mutations. | ||
| + | |||
| + | Structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations.,Yang ZF, Panwar P, McFarlane CR, Tuinte WE, Campiglio M, Van Petegem F Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2120416119. doi:, 10.1073/pnas.2120416119. Epub 2022 Mar 1. PMID:35238659<ref>PMID:35238659</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7rxe" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Panwar P]] | [[Category: Panwar P]] | ||
[[Category: Van Petegem F]] | [[Category: Van Petegem F]] | ||
[[Category: Yang Z]] | [[Category: Yang Z]] | ||
Current revision
Crystal structure of junctophilin-2
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