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| | <SX load='6cud' size='340' side='right' viewer='molstar' caption='[[6cud]], [[Resolution|resolution]] 3.30Å' scene=''> | | <SX load='6cud' size='340' side='right' viewer='molstar' caption='[[6cud]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6cud]] 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=6CUD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6CUD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cud]] 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=6CUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CUD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6OE:(2S)-3-{[(S)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-2-(HEXANOYLOXY)PROPYL+HEXANOATE'>6OE</scene>, <scene name='pdbligand=FGJ:(2R)-3-hydroxypropane-1,2-diyl+dihexanoate'>FGJ</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3.3Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6OE:(2S)-3-{[(S)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-2-(HEXANOYLOXY)PROPYL+HEXANOATE'>6OE</scene>, <scene name='pdbligand=FGJ:[(2~{R})-2-hexanoyloxy-3-oxidanyl-propyl]+hexanoate'>FGJ</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6cud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cud OCA], [http://pdbe.org/6cud PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cud RCSB], [http://www.ebi.ac.uk/pdbsum/6cud PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cud 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=6cud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cud OCA], [https://pdbe.org/6cud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cud RCSB], [https://www.ebi.ac.uk/pdbsum/6cud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cud 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Choi, W]] | + | [[Category: Choi W]] |
| - | [[Category: Du, J]] | + | [[Category: Du J]] |
| - | [[Category: Fan, C]] | + | [[Category: Fan C]] |
| - | [[Category: Lu, W]] | + | [[Category: Lu W]] |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Disease
TRPC3_HUMAN The disease is caused by mutations affecting the gene represented in this entry.
Function
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.[1] [2] [3] [4]
Publication Abstract from PubMed
The TRPC channels are crucially involved in store-operated calcium entry and calcium homeostasis, and they are implicated in human diseases such as neurodegenerative disease, cardiac hypertrophy, and spinocerebellar ataxia. We present a structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism from other TRP subfamily channels. The third transmembrane helix S3 is remarkably long, shaping a unique transmembrane domain, and constituting an extracellular domain that may serve as a sensor of external stimuli. We identified two lipid binding sites, one being sandwiched between the pre-S1 elbow and the S4-S5 linker, and the other being close to the ion-conducting pore, where the conserved LWF motif of the TRPC family is located.
Structure of the human lipid-gated cation channel TRPC3.,Fan C, Choi W, Sun W, Du J, Lu W Elife. 2018 May 4;7. pii: 36852. doi: 10.7554/eLife.36852. PMID:29726814[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Woo JS, Hwang JH, Ko JK, Weisleder N, Kim DH, Ma J, Lee EH. S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal muscle. Biochem J. 2010 Mar 15;427(1):125-34. doi: 10.1042/BJ20091225. PMID:20095964 doi:http://dx.doi.org/10.1042/BJ20091225
- ↑ Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell. 1996 May 31;85(5):661-71. PMID:8646775
- ↑ Zhu X, Jiang M, Birnbaumer L. Receptor-activated Ca2+ influx via human Trp3 stably expressed in human embryonic kidney (HEK)293 cells. Evidence for a non-capacitative Ca2+ entry. J Biol Chem. 1998 Jan 2;273(1):133-42. PMID:9417057
- ↑ Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 1999 Jan 21;397(6716):259-63. doi: 10.1038/16711. PMID:9930701 doi:http://dx.doi.org/10.1038/16711
- ↑ Fan C, Choi W, Sun W, Du J, Lu W. Structure of the human lipid-gated cation channel TRPC3. Elife. 2018 May 4;7. pii: 36852. doi: 10.7554/eLife.36852. PMID:29726814 doi:http://dx.doi.org/10.7554/eLife.36852
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