3im4

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{{STRUCTURE_3im4| PDB=3im4 | SCENE= }}
 
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===Crystal structure of cAMP-dependent Protein Kinase A Regulatory Subunit I alpha in complex with dual-specific A-Kinase Anchoring Protein 2===
 
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{{ABSTRACT_PUBMED_20159461}}
 
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==Disease==
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==Crystal structure of cAMP-dependent Protein Kinase A Regulatory Subunit I alpha in complex with dual-specific A-Kinase Anchoring Protein 2==
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[[http://www.uniprot.org/uniprot/AKA10_HUMAN AKA10_HUMAN]] Genetic variations in AKAP10 are a cause of susceptibility to sudden cardiac death (SCD) [MIM:[http://omim.org/entry/115080 115080]]. Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as chest pain and cardiac arrhythmias, particularly ventricular tachycardia, can lead to the loss of consciousness and cardiac arrest followed by biological death. Note=Increased susceptibility to sudden cardiac death may be conferred by AKAP10 variants that are associated with markers of low vagus nerve sensitivity, e.g. fast basal heart rate and low heart rate variability.<ref>PMID:17485678</ref>
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<StructureSection load='3im4' size='340' side='right'caption='[[3im4]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3im4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IM4 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.285&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3im4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3im4 OCA], [https://pdbe.org/3im4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3im4 RCSB], [https://www.ebi.ac.uk/pdbsum/3im4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3im4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KAP0_BOVIN KAP0_BOVIN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/3im4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3im4 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RIalpha D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RIIalpha:D-AKAP2 complex structure makes the mode of binding to RIalpha novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.
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==Function==
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Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.,Sarma GN, Kinderman FS, Kim C, von Daake S, Chen L, Wang BC, Taylor SS Structure. 2010 Feb 10;18(2):155-66. PMID:20159461<ref>PMID:20159461</ref>
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[[http://www.uniprot.org/uniprot/KAP0_BOVIN KAP0_BOVIN]] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. [[http://www.uniprot.org/uniprot/AKA10_HUMAN AKA10_HUMAN]] Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase (By similarity).
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3im4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IM4 OCA].
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</div>
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<div class="pdbe-citations 3im4" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]]
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*[[A-kinase anchor protein 3D structures|A-kinase anchor protein 3D structures]]
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*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:020159461</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Daake, S von.]]
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[[Category: Large Structures]]
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[[Category: Kim, C.]]
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[[Category: Kim C]]
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[[Category: Kinderman, F S.]]
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[[Category: Kinderman FS]]
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[[Category: Sarma, G N.]]
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[[Category: Sarma GN]]
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[[Category: Taylor, S S.]]
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[[Category: Taylor SS]]
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[[Category: Camp]]
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[[Category: Von Daake S]]
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[[Category: Camp-binding]]
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[[Category: Disulfide bond]]
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[[Category: Four-helix bundle]]
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[[Category: Membrane]]
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[[Category: Mitochondrion]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Signaling protein]]
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[[Category: Structural protein]]
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[[Category: Transit peptide]]
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Current revision

Crystal structure of cAMP-dependent Protein Kinase A Regulatory Subunit I alpha in complex with dual-specific A-Kinase Anchoring Protein 2

PDB ID 3im4

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