9ayf: Difference between revisions
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The | ==Structure of human calcium-sensing receptor in complex with Gi1 (miniGi1) protein in detergent== | ||
<StructureSection load='9ayf' size='340' side='right'caption='[[9ayf]], [[Resolution|resolution]] 3.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9ayf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9AYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9AYF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IG:3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]propan-1-amine'>9IG</scene>, <scene name='pdbligand=AV0:(2~{R},3~{R},4~{S},5~{S},6~{R})-2-[(2~{R},3~{S},4~{R},5~{R},6~{R})-6-[2-decyl-2-[[(2~{R},3~{R},4~{R},5~{S},6~{R})-6-(hydroxymethyl)-5-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-3,4-bis(oxidanyl)oxan-2-yl]oxymethyl]dodecoxy]-2-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol'>AV0</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TCR:CYCLOMETHYLTRYPTOPHAN'>TCR</scene></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=9ayf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ayf OCA], [https://pdbe.org/9ayf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ayf RCSB], [https://www.ebi.ac.uk/pdbsum/9ayf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ayf ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca(2+) concentration and maintains Ca(2+) homeostasis(1,2). It also mediates diverse cellular processes not associated with Ca(2+) balance(3-5). The functional pleiotropy of CaSR arises in part from its ability to signal through several G-protein subtypes(6). We determined structures of CaSR in complex with G proteins from three different subfamilies: G(q), G(i) and G(s). We found that the homodimeric CaSR of each complex couples to a single G protein through a common mode. This involves the C-terminal helix of each Galpha subunit binding to a shallow pocket that is formed in one CaSR subunit by all three intracellular loops (ICL1-ICL3), an extended transmembrane helix 3 and an ordered C-terminal region. G-protein binding expands the transmembrane dimer interface, which is further stabilized by phospholipid. The restraint imposed by the receptor dimer, in combination with ICL2, enables G-protein activation by facilitating conformational transition of Galpha. We identified a single Galpha residue that determines G(q) and G(s) versus G(i) selectivity. The length and flexibility of ICL2 allows CaSR to bind all three Galpha subtypes, thereby conferring capacity for promiscuous G-protein coupling. | |||
Promiscuous G-protein activation by the calcium-sensing receptor.,Zuo H, Park J, Frangaj A, Ye J, Lu G, Manning JJ, Asher WB, Lu Z, Hu GB, Wang L, Mendez J, Eng E, Zhang Z, Lin X, Grassucci R, Hendrickson WA, Clarke OB, Javitch JA, Conigrave AD, Fan QR Nature. 2024 May;629(8011):481-488. doi: 10.1038/s41586-024-07331-1. Epub 2024 , Apr 17. PMID:38632411<ref>PMID:38632411</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9ayf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Asher WB]] | |||
[[Category: Clarke OB]] | |||
[[Category: Conigrave AD]] | |||
[[Category: Eng E]] | |||
[[Category: Fan QR]] | |||
[[Category: Frangaj A]] | |||
[[Category: Grasucci R]] | |||
[[Category: Hendrickson WA]] | |||
[[Category: Hu G]] | |||
[[Category: Javitch JA]] | |||
[[Category: Lin X]] | |||
[[Category: Lu G]] | |||
[[Category: Lu Z]] | |||
[[Category: Manning JJ]] | |||
[[Category: Mendez J]] | |||
[[Category: Park J]] | |||
[[Category: Wang L]] | |||
[[Category: Ye J]] | |||
[[Category: Zhang Z]] | |||
[[Category: Zuo H]] | |||