6d7x

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(Difference between revisions)

Revision as of 10:00, 18 December 2019

Crystal Structure of Rat TRPV6*-Y466A- in complex with brominated 2-Aminoethoxydiphenyl borate (2-APB-Br)

Structural highlights

6d7x is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	Trpv6 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TRPV6_RAT] Calcium selective cation channel probably involved in Ca(2+) uptake in various tissues, including Ca(2+) reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:Q91WD2][UniProtKB:Q9H1D0]^[1]

Publication Abstract from PubMed

Transient receptor potential (TRP) channels are involved in various physiological processes, including sensory transduction. The TRP channel TRPV6 mediates calcium uptake in epithelia and its expression is dramatically increased in numerous types of cancer. TRPV6 inhibitors suppress tumor growth, but the molecular mechanism of inhibition remains unknown. Here, we present crystal and cryo-EM structures of human and rat TRPV6 bound to 2-aminoethoxydiphenyl borate (2-APB), a TRPV6 inhibitor and modulator of numerous TRP channels. 2-APB binds to TRPV6 in a pocket formed by the cytoplasmic half of the S1-S4 transmembrane helix bundle. Comparing human wild-type and high-affinity mutant Y467A structures, we show that 2-APB induces TRPV6 channel closure by modulating protein-lipid interactions. Mutagenesis and functional analyses suggest that the identified 2-APB binding site might be present in other members of vanilloid subfamily TRP channels. Our findings reveal a mechanism of ion channel allosteric modulation that can be exploited for therapeutic design.

Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB.,Singh AK, Saotome K, McGoldrick LL, Sobolevsky AI Nat Commun. 2018 Jun 25;9(1):2465. doi: 10.1038/s41467-018-04828-y. PMID:29941865^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yue L, Peng JB, Hediger MA, Clapham DE. CaT1 manifests the pore properties of the calcium-release-activated calcium channel. Nature. 2001 Apr 5;410(6829):705-9. PMID:11287959 doi:http://dx.doi.org/10.1038/35070596
↑ Singh AK, Saotome K, McGoldrick LL, Sobolevsky AI. Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB. Nat Commun. 2018 Jun 25;9(1):2465. doi: 10.1038/s41467-018-04828-y. PMID:29941865 doi:http://dx.doi.org/10.1038/s41467-018-04828-y

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6d7x"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Rat TRPV6*-Y466A- in complex with brominated 2-Aminoethoxydiphenyl borate (2-APB-Br)==
-<StructureSection load='6d7x' size='340' side='right' caption='[[6d7x]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+<StructureSection load='6d7x' size='340' side='right'caption='[[6d7x]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6d7x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D7X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6d7x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D7X FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DTB:6-(5-METHYL-2-OXO-IMIDAZOLIDIN-4-YL)-HEXANOIC+ACID'>DTB</scene>, <scene name='pdbligand=FYY:2-aminoethyl+(4-bromophenyl)phenylborinate'>FYY</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpv6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=6d7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7x OCA], [http://pdbe.org/6d7x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d7x RCSB], [http://www.ebi.ac.uk/pdbsum/6d7x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7x ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
+[[Category: Large Structures]]
 [[Category: McGoldrick, L L]]
 [[Category: Saotome, K]]

6d7x

From Proteopedia

Revision as of 10:00, 18 December 2019

Crystal Structure of Rat TRPV6*-Y466A- in complex with brominated 2-Aminoethoxydiphenyl borate (2-APB-Br)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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