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| | <SX load='6djs' size='340' side='right' viewer='molstar' caption='[[6djs]], [[Resolution|resolution]] 5.80Å' scene=''> | | <SX load='6djs' size='340' side='right' viewer='molstar' caption='[[6djs]], [[Resolution|resolution]] 5.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6djs]] is a 4 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=6DJS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DJS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6djs]] is a 4 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=6DJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DJS FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6djr|6djr]]</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=6djs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6djs OCA], [https://pdbe.org/6djs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6djs RCSB], [https://www.ebi.ac.uk/pdbsum/6djs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6djs ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPC3, TRP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6djs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6djs OCA], [http://pdbe.org/6djs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6djs RCSB], [http://www.ebi.ac.uk/pdbsum/6djs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6djs ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TRPC3_HUMAN TRPC3_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/TRPC3_HUMAN TRPC3_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRPC3_HUMAN TRPC3_HUMAN]] Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C, and by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May also be activated by internal calcium store depletion.<ref>PMID:20095964</ref> <ref>PMID:8646775</ref> <ref>PMID:9417057</ref> <ref>PMID:9930701</ref> | + | [https://www.uniprot.org/uniprot/TRPC3_HUMAN TRPC3_HUMAN] Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C, and by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May also be activated by internal calcium store depletion.<ref>PMID:20095964</ref> <ref>PMID:8646775</ref> <ref>PMID:9417057</ref> <ref>PMID:9930701</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The transient receptor potential ion channels support Ca(2+) permeation in many organs, including the heart, brain, and kidney. Genetic mutations in transient receptor potential cation channel subfamily C member 3 (TRPC3) are associated with neurodegenerative diseases, memory loss, and hypertension. To better understand the conformational changes that regulate TRPC3 function, we solved the cryo-EM structures for the full-length human TRPC3 and its cytoplasmic domain (CPD) in the apo state at 5.8 and 4.0 A resolution, respectively. These structures revealed that the TRPC3 transmembrane domain resembles those of other TRP channels and that the CPD is a stable module involved in channel assembly and gating. We observed the presence of a C-terminal domain swap at the center of the CPD, where horizontal helices (HHs) transition into a coiled-coil bundle. Comparison of TRPC3 structures revealed that the HHs can reside in two distinct positions. Electrophysiological analyses disclosed that shortening the length of the C-terminal loop connecting the HH with the TRP helices increases TRPC3 activity and that elongating the length of the loop has the opposite effect. Our findings indicate that the C-terminal loop affects channel gating by altering the allosteric coupling between the cytoplasmic and transmembrane domains. We propose that molecules that target the HH may represent a promising strategy for controlling TRPC3-associated neurological disorders and hypertension.
| + | |
| - | | + | |
| - | Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating.,Sierra-Valdez F, Azumaya CM, Romero LO, Nakagawa T, Cordero-Morales JF J Biol Chem. 2018 Aug 23. pii: RA118.005066. doi: 10.1074/jbc.RA118.005066. PMID:30139744<ref>PMID:30139744</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6djs" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Azumaya, C M]] | + | [[Category: Azumaya CM]] |
| - | [[Category: Cordero-Morales, J F]] | + | [[Category: Cordero-Morales JF]] |
| - | [[Category: Nakagawa, T]] | + | [[Category: Nakagawa T]] |
| - | [[Category: Sierra-Valdez, F J]] | + | [[Category: Sierra-Valdez FJ]] |
| - | [[Category: Cerebellum]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Moonwalker]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Trp channel]]
| + | |
