View source for 8buz


==Structure of Adenylyl cyclase 8 bound to stimulatory G-protein, Ca2+/Calmodulin, Forskolin and MANT-GTP==
<StructureSection load='8buz' size='340' side='right'caption='[[8buz]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8buz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BUZ 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]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FOK:FORSKOLIN'>FOK</scene>, <scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8buz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8buz OCA], [https://pdbe.org/8buz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8buz RCSB], [https://www.ebi.ac.uk/pdbsum/8buz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8buz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/E1BQ12_BOVIN E1BQ12_BOVIN] Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.[PIRNR:PIRNR039050]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Membrane adenylyl cyclase AC8 is regulated by G proteins and calmodulin (CaM), mediating the crosstalk between the cAMP pathway and Ca(2+) signalling. Despite the importance of AC8 in physiology, the structural basis of its regulation by G proteins and CaM is not well defined. Here, we report the 3.5 A resolution cryo-EM structure of the bovine AC8 bound to the stimulatory Galphas protein in the presence of Ca(2+)/CaM. The structure reveals the architecture of the ordered AC8 domains bound to Galphas and the small molecule activator forskolin. The extracellular surface of AC8 features a negatively charged pocket, a potential site for unknown interactors. Despite the well-resolved forskolin density, the captured state of AC8 does not favour tight nucleotide binding. The structural proteomics approaches, limited proteolysis and crosslinking mass spectrometry (LiP-MS and XL-MS), allowed us to identify the contact sites between AC8 and its regulators, CaM, Galphas, and Gbetagamma, as well as to infer the conformational changes induced by these interactions. Our results provide a framework for understanding the role of flexible regions in the mechanism of AC regulation.

Regulatory sites of CaM-sensitive adenylyl cyclase AC8 revealed by cryo-EM and structural proteomics.,Khanppnavar B, Schuster D, Lavriha P, Uliana F, Ozel M, Mehta V, Leitner A, Picotti P, Korkhov VM EMBO Rep. 2024 Mar;25(3):1513-1540. doi: 10.1038/s44319-024-00076-y. Epub 2024 , Feb 13. PMID:38351373<ref>PMID:38351373</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8buz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Khanppnavar B]]
[[Category: Korkhov VM]]
[[Category: Mehta V]]