View source for 6lpb


==Cryo-EM structure of the human PAC1 receptor coupled to an engineered heterotrimeric G protein==
<StructureSection load='6lpb' size='340' side='right'caption='[[6lpb]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lpb]] is a 6 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/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LPB 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]] 3.9&#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=6lpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lpb OCA], [https://pdbe.org/6lpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lpb RCSB], [https://www.ebi.ac.uk/pdbsum/6lpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lpb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PACA_HUMAN PACA_HUMAN] Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells.<ref>PMID:11175907</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide hormone. The PACAP receptor PAC1R, which belongs to the class B G-protein-coupled receptors (GPCRs), is a drug target for mental disorders and dry eye syndrome. Here, we present a cryo-EM structure of human PAC1R bound to PACAP and an engineered Gs heterotrimer. The structure revealed that transmembrane helix TM1 plays an essential role in PACAP recognition. The extracellular domain (ECD) of PAC1R tilts by ~40 degrees compared with that of the glucagon-like peptide-1 receptor (GLP-1R) and thus does not cover the peptide ligand. A functional analysis demonstrated that the PAC1R ECD functions as an affinity trap and is not required for receptor activation, whereas the GLP-1R ECD plays an indispensable role in receptor activation, illuminating the functional diversity of the ECDs in class B GPCRs. Our structural information will facilitate the design and improvement of better PAC1R agonists for clinical applications.

Cryo-EM structure of the human PAC1 receptor coupled to an engineered heterotrimeric G protein.,Kobayashi K, Shihoya W, Nishizawa T, Kadji FMN, Aoki J, Inoue A, Nureki O Nat Struct Mol Biol. 2020 Mar;27(3):274-280. doi: 10.1038/s41594-020-0386-8. Epub, 2020 Mar 9. PMID:32157248<ref>PMID:32157248</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lpb" 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: Unidentified]]
[[Category: Kobayashi K]]
[[Category: Nishizawa T]]
[[Category: Nureki O]]
[[Category: Shihoya W]]