7pd4: Difference between revisions

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</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=7pd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pd4 OCA], [https://pdbe.org/7pd4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pd4 RCSB], [https://www.ebi.ac.uk/pdbsum/7pd4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pd4 ProSAT]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Galphas subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Galphas complex provided the framework for understanding AC9 autoinhibition, the conformational changes that AC9 undergoes in response to activator binding remains poorly understood. Here, we present the cryo-EM structures of AC9 in several distinct states: (i) AC9 bound to a nucleotide inhibitor MANT-GTP, (ii) bound to an artificial activator (DARPin C4) and MANT-GTP, (iii) bound to DARPin C4 and a nucleotide analogue ATPalphaS, (iv) bound to Galphas and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Galphas binding site. Together with the previously observed occluded and forskolin-bound conformations, structural comparisons of AC9 in the four conformations described here show that secondary structure rearrangements in the region surrounding the forskolin binding site are essential for AC9 activation.

Structural basis of adenylyl cyclase 9 activation.,Qi C, Lavriha P, Mehta V, Khanppnavar B, Mohammed I, Li Y, Lazaratos M, Schaefer JV, Dreier B, Pluckthun A, Bondar AN, Dessauer CW, Korkhov VM Nat Commun. 2022 Feb 24;13(1):1045. doi: 10.1038/s41467-022-28685-y. PMID:35210418<ref>PMID:35210418</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

== References ==

__TOC__

</StructureSection>

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 </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=7pd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pd4 OCA], [https://pdbe.org/7pd4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pd4 RCSB], [https://www.ebi.ac.uk/pdbsum/7pd4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pd4 ProSAT]</span></td></tr>
 </table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Galphas subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Galphas complex provided the framework for understanding AC9 autoinhibition, the conformational changes that AC9 undergoes in response to activator binding remains poorly understood. Here, we present the cryo-EM structures of AC9 in several distinct states: (i) AC9 bound to a nucleotide inhibitor MANT-GTP, (ii) bound to an artificial activator (DARPin C4) and MANT-GTP, (iii) bound to DARPin C4 and a nucleotide analogue ATPalphaS, (iv) bound to Galphas and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Galphas binding site. Together with the previously observed occluded and forskolin-bound conformations, structural comparisons of AC9 in the four conformations described here show that secondary structure rearrangements in the region surrounding the forskolin binding site are essential for AC9 activation.
+Structural basis of adenylyl cyclase 9 activation.,Qi C, Lavriha P, Mehta V, Khanppnavar B, Mohammed I, Li Y, Lazaratos M, Schaefer JV, Dreier B, Pluckthun A, Bondar AN, Dessauer CW, Korkhov VM Nat Commun. 2022 Feb 24;13(1):1045. doi: 10.1038/s41467-022-28685-y. PMID:35210418<ref>PMID:35210418</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7pd4" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>