6d7l
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6d7l' size='340' side='right' caption='[[6d7l]], [[Resolution|resolution]] 4.00Å' scene=''> | <StructureSection load='6d7l' size='340' side='right' caption='[[6d7l]], [[Resolution|resolution]] 4.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6d7l]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D7L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d7l]] 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=6D7L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D7L 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=6d7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7l OCA], [http://pdbe.org/6d7l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d7l RCSB], [http://www.ebi.ac.uk/pdbsum/6d7l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7l ProSAT]</span></td></tr> | + | </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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6d7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7l OCA], [http://pdbe.org/6d7l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d7l RCSB], [http://www.ebi.ac.uk/pdbsum/6d7l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| Line 10: | Line 11: | ||
== 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> | [[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 == | ||
| + | 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 6d7l" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Azumaya, C M]] | [[Category: Azumaya, C M]] | ||
[[Category: Cordero-Morales, J F]] | [[Category: Cordero-Morales, J F]] | ||
Revision as of 10:28, 5 September 2018
Cytoplasmic domain of TRPC3
| |||||||||||
