|
|
| Line 3: |
Line 3: |
| | <SX load='5yx9' size='340' side='right' viewer='molstar' caption='[[5yx9]], [[Resolution|resolution]] 3.80Å' scene=''> | | <SX load='5yx9' size='340' side='right' viewer='molstar' caption='[[5yx9]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yx9]] 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=5YX9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5YX9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yx9]] 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=5YX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YX9 FirstGlance]. <br> |
| - | </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=5yx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yx9 OCA], [http://pdbe.org/5yx9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yx9 RCSB], [http://www.ebi.ac.uk/pdbsum/5yx9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yx9 ProSAT]</span></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'>[https://proteopedia.org/fgij/fg.htm?mol=5yx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yx9 OCA], [https://pdbe.org/5yx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yx9 RCSB], [https://www.ebi.ac.uk/pdbsum/5yx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yx9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TRPC6_HUMAN TRPC6_HUMAN]] Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/TRPC6_HUMAN TRPC6_HUMAN] Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRPC6_HUMAN TRPC6_HUMAN]] Thought to form a receptor-activated non-selective calcium permeant cation channel (PubMed:19936226, PubMed:23291369). 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 (PubMed:26892346). Seems not to be activated by intracellular calcium store depletion.<ref>PMID:19936226</ref> <ref>PMID:23291369</ref> <ref>PMID:26892346</ref> | + | [https://www.uniprot.org/uniprot/TRPC6_HUMAN TRPC6_HUMAN] Thought to form a receptor-activated non-selective calcium permeant cation channel (PubMed:19936226, PubMed:23291369). 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 (PubMed:26892346). Seems not to be activated by intracellular calcium store depletion.<ref>PMID:19936226</ref> <ref>PMID:23291369</ref> <ref>PMID:26892346</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | TRPC6 and TRPC3 are receptor-activated nonselective cation channels that belong to the family of canonical transient receptor potential (TRPC) channels. They are activated by diacylglycerol, a lipid second messenger. TRPC6 and TRPC3 are involved in many physiological processes and implicated in human genetic diseases. Here we present the structure of human TRPC6 homotetramer in complex with a newly identified high-affinity inhibitor BTDM solved by single-particle cryo-electron microscopy to 3.8 A resolution. We also present the structure of human TRPC3 at 4.4 A resolution. These structures show two-layer architectures in which the bell-shaped cytosolic layer holds the transmembrane layer. Extensive inter-subunit interactions of cytosolic domains, including the N-terminal ankyrin repeats and the C-terminal coiled-coil, contribute to the tetramer assembly. The high-affinity inhibitor BTDM wedges between the S5-S6 pore domain and voltage sensor-like domain to inhibit channel opening. Our structures uncover the molecular architecture of TRPC channels and provide a structural basis for understanding the mechanism of these channels.
| + | |
| - | | + | |
| - | Structure of the receptor-activated human TRPC6 and TRPC3 ion channels.,Tang Q, Guo W, Zheng L, Wu JX, Liu M, Zhou X, Zhang X, Chen L Cell Res. 2018 Apr 26. pii: 10.1038/s41422-018-0038-2. doi:, 10.1038/s41422-018-0038-2. PMID:29700422<ref>PMID:29700422</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5yx9" 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: Chen, L]] | + | [[Category: Chen L]] |
| - | [[Category: Guo, W]] | + | [[Category: Guo W]] |
| - | [[Category: Tang, Q]] | + | [[Category: Tang Q]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Trpc6 channel]]
| + | |
| Structural highlights
Disease
TRPC6_HUMAN Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis. The disease is caused by mutations affecting the gene represented in this entry.
Function
TRPC6_HUMAN Thought to form a receptor-activated non-selective calcium permeant cation channel (PubMed:19936226, PubMed:23291369). 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 (PubMed:26892346). Seems not to be activated by intracellular calcium store depletion.[1] [2] [3]
References
- ↑ Heeringa SF, Moller CC, Du J, Yue L, Hinkes B, Chernin G, Vlangos CN, Hoyer PF, Reiser J, Hildebrandt F. A novel TRPC6 mutation that causes childhood FSGS. PLoS One. 2009 Nov 10;4(11):e7771. doi: 10.1371/journal.pone.0007771. PMID:19936226 doi:http://dx.doi.org/10.1371/journal.pone.0007771
- ↑ Hofstra JM, Lainez S, van Kuijk WH, Schoots J, Baltissen MP, Hoefsloot LH, Knoers NV, Berden JH, Bindels RJ, van der Vlag J, Hoenderop JG, Wetzels JF, Nijenhuis T. New TRPC6 gain-of-function mutation in a non-consanguineous Dutch family with late-onset focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2013 Jul;28(7):1830-8. doi: 10.1093/ndt/gfs572. Epub, 2013 Jan 4. PMID:23291369 doi:http://dx.doi.org/10.1093/ndt/gfs572
- ↑ Riehle M, Buscher AK, Gohlke BO, Kassmann M, Kolatsi-Joannou M, Brasen JH, Nagel M, Becker JU, Winyard P, Hoyer PF, Preissner R, Krautwurst D, Gollasch M, Weber S, Harteneck C. TRPC6 G757D Loss-of-Function Mutation Associates with FSGS. J Am Soc Nephrol. 2016 Sep;27(9):2771-83. doi: 10.1681/ASN.2015030318. Epub 2016 , Feb 18. PMID:26892346 doi:http://dx.doi.org/10.1681/ASN.2015030318
|
