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3im4

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Revision as of 09:32, 19 December 2018

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

Structural highlights

3im4 is a 3 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3im3
Gene:	PRKAR1A (BOVIN), AKAP10 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[AKA10_HUMAN] Genetic variations in AKAP10 are a cause of susceptibility to sudden cardiac death (SCD) [MIM: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.^[1]

Function

[KAP0_BOVIN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. [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).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[2]

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

References

↑ Tingley WG, Pawlikowska L, Zaroff JG, Kim T, Nguyen T, Young SG, Vranizan K, Kwok PY, Whooley MA, Conklin BR. Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8461-6. Epub 2007 May 7. PMID:17485678 doi:10.1073/pnas.0610393104
↑ Sarma GN, Kinderman FS, Kim C, von Daake S, Chen L, Wang BC, Taylor SS. Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity. Structure. 2010 Feb 10;18(2):155-66. PMID:20159461 doi:10.1016/j.str.2009.12.012

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3im4"

@@ Line 1: / Line 1: @@
 ==Crystal structure of cAMP-dependent Protein Kinase A Regulatory Subunit I alpha in complex with dual-specific A-Kinase Anchoring Protein 2==
 <StructureSection load='3im4' size='340' side='right' caption='[[3im4]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3im3|3im3]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAR1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), AKAP10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3im4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3im4 OCA], [http://pdbe.org/3im4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3im4 RCSB], [http://www.ebi.ac.uk/pdbsum/3im4 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3im4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3im4 OCA], [http://pdbe.org/3im4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3im4 RCSB], [http://www.ebi.ac.uk/pdbsum/3im4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3im4 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/3im4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/3im4_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 33: / Line 34: @@
 ==See Also==
+*[[A-kinase anchor protein|A-kinase anchor protein]]
 *[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]]
 == References ==
@@ Line 45: / Line 47: @@
 [[Category: Sarma, G N]]
 [[Category: Taylor, S S]]
+[[Category: Acetylation]]
 [[Category: Camp]]
 [[Category: Camp-binding]]
+[[Category: Cytoplasm]]
 [[Category: Disulfide bond]]
 [[Category: Four-helix bundle]]
@@ Line 53: / Line 57: @@
 [[Category: Nucleotide-binding]]
 [[Category: Phosphoprotein]]
+[[Category: Polymorphism]]
 [[Category: Signaling protein]]
 [[Category: Structural protein]]
 [[Category: Transit peptide]]

3im4

From Proteopedia

Revision as of 09:32, 19 December 2018

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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