View source for 7v9l


==Cryo-EM structure of the SV1-Gs complex.==
<StructureSection load='7v9l' size='340' side='right'caption='[[7v9l]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7v9l]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7V9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V9L 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]] 2.6&#8491;</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=7v9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v9l OCA], [https://pdbe.org/7v9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v9l RCSB], [https://www.ebi.ac.uk/pdbsum/7v9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v9l ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9HB45_HUMAN Q9HB45_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates G(s) while SV1 selectively couples to beta-arrestins. Based on the cryogenic electron microscopy structures of SV1 in the apo state or GHRH-bound state in complex with the G(s) protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, G(s) versus beta-arrestins. As suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias toward beta-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation.

Constitutive signal bias mediated by the human GHRHR splice variant 1.,Cong Z, Zhou F, Zhang C, Zou X, Zhang H, Wang Y, Zhou Q, Cai X, Liu Q, Li J, Shao L, Mao C, Wang X, Wu J, Xia T, Zhao LH, Jiang H, Zhang Y, Xu HE, Cheng X, Yang D, Wang MW Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):e2106606118. doi: , 10.1073/pnas.2106606118. PMID:34599099<ref>PMID:34599099</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7v9l" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Synthetic construct]]
[[Category: Cai XQ]]
[[Category: Cheng X]]
[[Category: Cong ZT]]
[[Category: Jiang HL]]
[[Category: Li J]]
[[Category: Liu QF]]
[[Category: Mao CY]]
[[Category: Shao LJ]]
[[Category: Wang MW]]
[[Category: Wang X]]
[[Category: Wang YZ]]
[[Category: Wu JH]]
[[Category: Xia T]]
[[Category: Xu HE]]
[[Category: Yang DH]]
[[Category: Zhang C]]
[[Category: Zhang HB]]
[[Category: Zhang Y]]
[[Category: Zhao LH]]
[[Category: Zhou FL]]
[[Category: Zhou QT]]
[[Category: Zou XY]]