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4wbb

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Single Turnover Autophosphorylation Cycle of the PKA RIIb Holoenzyme

Structural highlights

4wbb is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAP3_MOUSE Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.

Publication Abstract from PubMed

To provide tight spatiotemporal signaling control, the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme typically nucleates a macromolecular complex or a "PKA signalosome." Using the RIIbeta holoenzyme as a prototype, we show how autophosphorylation/dephosphorylation of the RIIbeta subunit, as well as cAMP and metal ions, contribute to the dynamics of PKA signaling. While we showed previously that the RIIbeta holoenzyme could undergo a single turnover autophosphorylation with adenosine triphosphate and magnesium (MgATP) and trap both products in the crystal lattice, we asked here whether calcium could trap an ATP:RIIbeta holoenzyme since the RIIbeta holoenzyme is located close to ion channels. The 2.8A structure of an RIIbetap2:C2:(Ca2ADP)2 holoenzyme, supported by biochemical and biophysical data, reveals a trapped single phosphorylation event similar to MgATP. Thus, calcium can mediate a single turnover event with either ATP or adenosine-5'-(beta,gamma-imido)triphosphate (AMP-PNP), even though it cannot support steady-state catalysis efficiently. The holoenzyme serves as a "product trap" because of the slow off-rate of the pRIIbeta subunit, which is controlled by cAMP, not by phosphorylation of the inhibitor site. By quantitatively defining the RIIbeta signaling cycle, we show that release of pRIIbeta in the presence of cAMP is reduced by calcium, whereas autophosphorylation at the phosphorylation site (P-site) inhibits holoenzyme reassociation with the catalytic subunit. Adding a single phosphoryl group to the preformed RIIbeta holoenzyme thus creates a signaling cycle in which phosphatases become an essential partner. This previously unappreciated molecular mechanism is an integral part of PKA signaling for type II holoenzymes.

Single Turnover Autophosphorylation Cycle of the PKA RIIbeta Holoenzyme.,Zhang P, Knape MJ, Ahuja LG, Keshwani MM, King CC, Sastri M, Herberg FW, Taylor SS PLoS Biol. 2015 Jul 9;13(7):e1002192. doi: 10.1371/journal.pbio.1002192., eCollection 2015 Jul. PMID:26158466^[1]

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

References

↑ Zhang P, Knape MJ, Ahuja LG, Keshwani MM, King CC, Sastri M, Herberg FW, Taylor SS. Single Turnover Autophosphorylation Cycle of the PKA RIIbeta Holoenzyme. PLoS Biol. 2015 Jul 9;13(7):e1002192. doi: 10.1371/journal.pbio.1002192., eCollection 2015 Jul. PMID:26158466 doi:http://dx.doi.org/10.1371/journal.pbio.1002192

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4wbb"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4wbb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WBB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=4wbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wbb OCA], [https://pdbe.org/4wbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wbb RCSB], [https://www.ebi.ac.uk/pdbsum/4wbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wbb ProSAT]</span></td></tr>
 </table>

4wbb

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Current revision

Single Turnover Autophosphorylation Cycle of the PKA RIIb Holoenzyme

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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