5zbg

From Proteopedia

(Difference between revisions)

Revision as of 06:14, 9 May 2018

Cryo-EM structure of human TRPC3 at 4.36A resolution

Structural highlights

5zbg is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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^[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
↑ Tang Q, Guo W, Zheng L, Wu JX, Liu M, Zhou X, Zhang X, Chen L. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Cell Res. 2018 Apr 26. pii: 10.1038/s41422-018-0038-2. doi:, 10.1038/s41422-018-0038-2. PMID:29700422 doi:http://dx.doi.org/10.1038/s41422-018-0038-2

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5zbg"

Categories: Chen, L | Guo, W | Tang, Q | Membrane protein | Trpc3 channel

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5zbg is ON HOLD  until Paper Publication
+==Cryo-EM structure of human TRPC3 at 4.36A resolution==
+<StructureSection load='5zbg' size='340' side='right' caption='[[5zbg]], [[Resolution|resolution]] 4.36&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5zbg]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZBG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZBG FirstGlance]. <br>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zbg OCA], [http://pdbe.org/5zbg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zbg RCSB], [http://www.ebi.ac.uk/pdbsum/5zbg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zbg ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/TRPC3_HUMAN TRPC3_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.
+== 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>
+<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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5zbg" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Chen, L]]
+[[Category: Guo, W]]
+[[Category: Tang, Q]]
+[[Category: Membrane protein]]
+[[Category: Trpc3 channel]]

5zbg

From Proteopedia

Revision as of 06:14, 9 May 2018

Cryo-EM structure of human TRPC3 at 4.36A resolution

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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