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| | <SX load='6cv9' size='340' side='right' viewer='molstar' caption='[[6cv9]], [[Resolution|resolution]] 3.80Å' scene=''> | | <SX load='6cv9' size='340' side='right' viewer='molstar' caption='[[6cv9]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6cv9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CV9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6CV9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cv9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CV9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CV9 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpc6, Trp6, Trrp6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 3.8Å</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=6cv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cv9 OCA], [http://pdbe.org/6cv9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cv9 RCSB], [http://www.ebi.ac.uk/pdbsum/6cv9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cv9 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=6cv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cv9 OCA], [https://pdbe.org/6cv9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cv9 RCSB], [https://www.ebi.ac.uk/pdbsum/6cv9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cv9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRPC6_MOUSE TRPC6_MOUSE]] 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. Seems not to be activated by intracellular calcium store depletion.[UniProtKB:Q9Y210] | + | [https://www.uniprot.org/uniprot/TRPC6_MOUSE TRPC6_MOUSE] 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. Seems not to be activated by intracellular calcium store depletion.[UniProtKB:Q9Y210] |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filter, whose damage leads to progressive kidney failure and focal segmental glomerulosclerosis (FSGS). The canonical transient receptor potential 6 (TRPC6) ion channel is expressed in the podocyte and mutations in its cytoplasmic domain cause FSGS in humans. In vitro evaluation of disease-causing mutations in TRPC6 has revealed that these genetic alterations result in abnormal ion channel gating. However, the mechanism whereby the cytoplasmic domain modulates TRPC6 function is largely unknown. Here we report a cryoEM structure of the cytoplasmic domain of murine TRPC6 at 3.8A resolution. The cytoplasmic fold of TRPC6 is characterized by an inverted dome-like chamber pierced by four radial horizontal helices that converge into a vertical coiled-coil at the central axis. Unlike in other TRP channels, TRPC6 displays a unique domain swap that occurs at the junction of the horizontal helices and coiled-coil. Multiple FSGS mutations converge at the buried interface between the vertical coiled-coil and the ankyrin repeats, which form the dome, suggesting these regions are critical for allosteric gating modulation. This functionally critical interface is a potential target for drug design. Importantly, dysfunction in other family members leads to learning deficits (TRPC1/4/5) and ataxia (TRPC3). Our data provide a structural framework for the mechanistic investigation of the TRPC family.
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| - | | + | |
| - | Cryo-EM structure of the cytoplasmic domain of murine transient receptor potential cation channel subfamily C member 6 (TRPC6).,Azumaya CM, Sierra-Valdez F, Cordero-Morales JF, Nakagawa T J Biol Chem. 2018 May 11. pii: RA118.003183. doi: 10.1074/jbc.RA118.003183. PMID:29752403<ref>PMID:29752403</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6cv9" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[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: Focal segmental glomerulosclerosis]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Trp channel]]
| + | |
| - | [[Category: Trpc6]]
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