6dmu: Difference between revisions
No edit summary |
No edit summary |
||
Line 1: | Line 1: | ||
The | ==PI(4,5)P2 bound full-length rbTRPV5== | ||
<SX load='6dmu' size='340' side='right' viewer='molstar' caption='[[6dmu]], [[Resolution|resolution]] 4.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6dmu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DMU FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpv5, Ecac1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</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=6dmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dmu OCA], [http://pdbe.org/6dmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dmu RCSB], [http://www.ebi.ac.uk/pdbsum/6dmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dmu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/TRPV5_RABIT TRPV5_RABIT]] Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5]<ref>PMID:10085067</ref> <ref>PMID:11035011</ref> <ref>PMID:12574114</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-pi interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery. | |||
Structural insights on TRPV5 gating by endogenous modulators.,Hughes TET, Pumroy RA, Yazici AT, Kasimova MA, Fluck EC, Huynh KW, Samanta A, Molugu SK, Zhou ZH, Carnevale V, Rohacs T, Moiseenkova-Bell VY Nat Commun. 2018 Oct 10;9(1):4198. doi: 10.1038/s41467-018-06753-6. PMID:30305626<ref>PMID:30305626</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Hughes, T | <div class="pdbe-citations 6dmu" style="background-color:#fffaf0;"></div> | ||
[[Category: Moiseenkova-Bell, V | == References == | ||
[[Category: Pumroy, R | <references/> | ||
__TOC__ | |||
</SX> | |||
[[Category: European rabbit]] | |||
[[Category: Large Structures]] | |||
[[Category: Hughes, T E.T]] | |||
[[Category: Moiseenkova-Bell, V Y]] | |||
[[Category: Pumroy, R A]] | |||
[[Category: Full-length]] | |||
[[Category: Ion channel]] | |||
[[Category: Transport protein]] | |||
[[Category: Trpv5]] |