View source for 9bip


==Human proton sensing receptor GPR4 in complex with miniGs==
<StructureSection load='9bip' size='340' side='right'caption='[[9bip]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bip]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BIP 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]] 2.8&#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=9bip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bip OCA], [https://pdbe.org/9bip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bip RCSB], [https://www.ebi.ac.uk/pdbsum/9bip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bip ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Three proton-sensing G protein-coupled receptors (GPCRs)-GPR4, GPR65, and GPR68-respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues. Using deep mutational scanning (DMS), we determined the functional importance of every residue in GPR68 activation by generating approximately 9,500 mutants and measuring their effects on signaling and surface expression. Constant-pH molecular dynamics simulations provided insights into the conformational landscape and protonation patterns of key residues. This unbiased approach revealed that, unlike other proton-sensitive channels and receptors, no single site is critical for proton recognition. Instead, a network of titratable residues extends from the extracellular surface to the transmembrane region, converging on canonical motifs to activate proton-sensing GPCRs. Our approach integrating structure, simulations, and unbiased functional interrogation provides a framework for understanding GPCR signaling complexity.

Molecular basis of proton sensing by G protein-coupled receptors.,Howard MK, Hoppe N, Huang XP, Mitrovic D, Billesbolle CB, Macdonald CB, Mehrotra E, Rockefeller Grimes P, Trinidad DD, Delemotte L, English JG, Coyote-Maestas W, Manglik A Cell. 2024 Dec 26:S0092-8674(24)01373-4. doi: 10.1016/j.cell.2024.11.036. PMID:39753132<ref>PMID:39753132</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bip" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Coyote-Maestas W]]
[[Category: English J]]
[[Category: Hoppe N]]
[[Category: Howard MK]]
[[Category: Huang XP]]
[[Category: Macdonald CB]]
[[Category: Manglik A]]
[[Category: Mehrotra E]]
[[Category: Rockefeller Grimes P]]
[[Category: Trinidad DD]]
[[Category: Zahm AM]]