1l6e: Difference between revisions

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~~[[Image:1l6e.gif|left|200px]]<br /><applet load="1l6e" size="450" color="white" frame="true" align="right" spinBox="true"~~

~~caption="1l6e" />~~

'''Solution structure of the docking and dimerization domain of protein kinase A II-alpha (RIIalpha D/D). Alternatively called the N-terminal dimerization domain of the regulatory subunit of protein kinase A.'''<br />

==~~Overview~~==

==Solution structure of the docking and dimerization domain of protein kinase A II-alpha (RIIalpha D/D). Alternatively called the N-terminal dimerization domain of the regulatory subunit of protein kinase A.==

The structure of the N-terminal docking and dimerization domain of the, type IIalpha regulatory subunit (RIIalpha D/D) of protein kinase A (PKA), forms a noncovalent stand-alone X-type four-helix bundle structural motif, consisting of two helix-loop-helix monomers. RIIalpha D/D possesses a, strong hydrophobic core and two distinct, exposed faces. A hydrophobic, face with a groove is the site of protein-protein interactions necessary, for subcellular localization. A highly charged face, opposite to the, former, may be involved in regulation of protein-protein interactions as a, result of changes in phosphorylation state of the regulatory subunit., Although recent studies have addressed the hydrophobic character of, packing of RIIalpha D/D and revealed the function of the hydrophobic face, as the binding site to A-kinase anchoring proteins (AKAPs), little, attention has been paid to the charges involved in structure and function., To examine the electrostatic character of the structure of RIIalpha D/D we, have predicted mean apparent pKa values, based on Poisson-Boltzmann, electrostatic calculations, using an ensemble of calculated dimer, structures. We propose that the helix promoting sequence Glu34-X-X-X-Arg38, stabilizes the second helix of each monomer, through the formation of a, (i, i +4) side chain salt bridge. We show that a weak inter-helical, hydrogen bond between Tyr35-Glu19 of each monomer contributes to tertiary, packing and may be responsible for discriminating from alternative, quaternary packing of the two monomers. We also show that an inter-monomer, hydrogen bond between Asp30-Arg40 contributes to quaternary packing. We, propose that the charged face comprising of, Asp27-Asp30-Glu34-Arg38-Arg40-Glu41-Arg43-Arg44 may be necessary to, provide flexibility or stability in the region between the C-terminus and, the interdomain/autoinhibitory sequence of RIIalpha, depending on the, activation state of PKA. We also discuss the structural requirements, necessary for the formation of a stacked (rather than intertwined) dimer, which has consequences for the orientation of the functionally important, and distinct faces.

== Structural highlights ==

<table><tr><td colspan='2'>[[1l6e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L6E FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1l6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l6e OCA], [https://pdbe.org/1l6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l6e RCSB], [https://www.ebi.ac.uk/pdbsum/1l6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l6e ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/KAP2_MOUSE KAP2_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.

== Evolutionary Conservation ==

[[Image:Consurf_key_small.gif|200px|right]]

Check<jmol>

<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l6/1l6e_consurf.spt"</scriptWhenChecked>

<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>

<text>to colour the structure by Evolutionary Conservation</text>

</jmolCheckbox>

</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=1l6e ConSurf].

== Publication Abstract from PubMed ==

The structure of the N-terminal docking and dimerization domain of the type IIalpha regulatory subunit (RIIalpha D/D) of protein kinase A (PKA) forms a noncovalent stand-alone X-type four-helix bundle structural motif, consisting of two helix-loop-helix monomers. RIIalpha D/D possesses a strong hydrophobic core and two distinct, exposed faces. A hydrophobic face with a groove is the site of protein-protein interactions necessary for subcellular localization. A highly charged face, opposite to the former, may be involved in regulation of protein-protein interactions as a result of changes in phosphorylation state of the regulatory subunit. Although recent studies have addressed the hydrophobic character of packing of RIIalpha D/D and revealed the function of the hydrophobic face as the binding site to A-kinase anchoring proteins (AKAPs), little attention has been paid to the charges involved in structure and function. To examine the electrostatic character of the structure of RIIalpha D/D we have predicted mean apparent pKa values, based on Poisson-Boltzmann electrostatic calculations, using an ensemble of calculated dimer structures. We propose that the helix promoting sequence Glu34-X-X-X-Arg38 stabilizes the second helix of each monomer, through the formation of a (i, i +4) side chain salt bridge. We show that a weak inter-helical hydrogen bond between Tyr35-Glu19 of each monomer contributes to tertiary packing and may be responsible for discriminating from alternative quaternary packing of the two monomers. We also show that an inter-monomer hydrogen bond between Asp30-Arg40 contributes to quaternary packing. We propose that the charged face comprising of Asp27-Asp30-Glu34-Arg38-Arg40-Glu41-Arg43-Arg44 may be necessary to provide flexibility or stability in the region between the C-terminus and the interdomain/autoinhibitory sequence of RIIalpha, depending on the activation state of PKA. We also discuss the structural requirements necessary for the formation of a stacked (rather than intertwined) dimer, which has consequences for the orientation of the functionally important and distinct faces.

~~==About this Structure==~~

Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha.,Morikis D, Roy M, Newlon MG, Scott JD, Jennings PA Eur J Biochem. 2002 Apr;269(8):2040-51. PMID:11985580<ref>PMID:11985580</ref>

~~1L6E is a [http://en.wikipedia.org/wiki/Single_protein Single protein]~~ structure of ~~sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine~~ protein kinase], ~~with EC number [http~~:~~//www.brenda~~-~~enzymes~~.~~info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http~~:/~~/ispc.weizmann.ac.il/oca-bin/ocashort?id=1L6E OCA].~~

==~~Reference~~==

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

~~Electrostatic properties of the structure of the docking and dimerization domain of~~ protein kinase ~~A IIalpha., Morikis D, Roy M, Newlon MG, Scott JD, Jennings PA, Eur J Biochem. 2002 Apr;269(8):2040~~-~~51. PMID:~~[~~http~~:~~//ispc.weizmann.ac.il//pmbin/getpm?pmid=11985580 11985580~~]

</div>

==See Also==

*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Mus musculus]]

~~[[Category: Non-specific serine/threonine protein kinase]]~~

[[Category: Jennings PA]]

~~[[Category: Single protein]]~~

[[Category: Morikis D]]

[[Category: Jennings~~, P.A.~~]]

[[Category: Newlon MG]]

[[Category: Morikis, D.]]

[[Category: Roy M]]

[[Category: Newlon~~, M.G.~~]]

[[Category: Scott JD]]

[[Category: Roy, M.]]

[[Category: Scott~~, J.D.~~]]

~~[[Category: anchoring]]~~

~~[[Category: dimerization]]~~

~~[[Category: docking]]~~

~~[[Category: four-helix bundle]]~~

~~[[Category: helix-loop-helix]]~~

~~[[Category: regulatory subunit]]~~

~~''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:18:49 2007''~~

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@@ Line 1: / Line 1: @@
-[[Image:1l6e.gif|left|200px]]<br /><applet load="1l6e" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1l6e" />
-'''Solution structure of the docking and dimerization domain of protein kinase A II-alpha (RIIalpha D/D). Alternatively called the N-terminal dimerization domain of the regulatory subunit of protein kinase A.'''<br />
-==Overview==
+==Solution structure of the docking and dimerization domain of protein kinase A II-alpha (RIIalpha D/D). Alternatively called the N-terminal dimerization domain of the regulatory subunit of protein kinase A.==
-The structure of the N-terminal docking and dimerization domain of the, type IIalpha regulatory subunit (RIIalpha D/D) of protein kinase A (PKA), forms a noncovalent stand-alone X-type four-helix bundle structural motif, consisting of two helix-loop-helix monomers. RIIalpha D/D possesses a, strong hydrophobic core and two distinct, exposed faces. A hydrophobic, face with a groove is the site of protein-protein interactions necessary, for subcellular localization. A highly charged face, opposite to the, former, may be involved in regulation of protein-protein interactions as a, result of changes in phosphorylation state of the regulatory subunit., Although recent studies have addressed the hydrophobic character of, packing of RIIalpha D/D and revealed the function of the hydrophobic face, as the binding site to A-kinase anchoring proteins (AKAPs), little, attention has been paid to the charges involved in structure and function., To examine the electrostatic character of the structure of RIIalpha D/D we, have predicted mean apparent pKa values, based on Poisson-Boltzmann, electrostatic calculations, using an ensemble of calculated dimer, structures. We propose that the helix promoting sequence Glu34-X-X-X-Arg38, stabilizes the second helix of each monomer, through the formation of a, (i, i +4) side chain salt bridge. We show that a weak inter-helical, hydrogen bond between Tyr35-Glu19 of each monomer contributes to tertiary, packing and may be responsible for discriminating from alternative, quaternary packing of the two monomers. We also show that an inter-monomer, hydrogen bond between Asp30-Arg40 contributes to quaternary packing. We, propose that the charged face comprising of, Asp27-Asp30-Glu34-Arg38-Arg40-Glu41-Arg43-Arg44 may be necessary to, provide flexibility or stability in the region between the C-terminus and, the interdomain/autoinhibitory sequence of RIIalpha, depending on the, activation state of PKA. We also discuss the structural requirements, necessary for the formation of a stacked (rather than intertwined) dimer, which has consequences for the orientation of the functionally important, and distinct faces.
+<StructureSection load='1l6e' size='340' side='right'caption='[[1l6e]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1l6e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L6E FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1l6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l6e OCA], [https://pdbe.org/1l6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l6e RCSB], [https://www.ebi.ac.uk/pdbsum/1l6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l6e ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KAP2_MOUSE KAP2_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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l6/1l6e_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1l6e ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The structure of the N-terminal docking and dimerization domain of the type IIalpha regulatory subunit (RIIalpha D/D) of protein kinase A (PKA) forms a noncovalent stand-alone X-type four-helix bundle structural motif, consisting of two helix-loop-helix monomers. RIIalpha D/D possesses a strong hydrophobic core and two distinct, exposed faces. A hydrophobic face with a groove is the site of protein-protein interactions necessary for subcellular localization. A highly charged face, opposite to the former, may be involved in regulation of protein-protein interactions as a result of changes in phosphorylation state of the regulatory subunit. Although recent studies have addressed the hydrophobic character of packing of RIIalpha D/D and revealed the function of the hydrophobic face as the binding site to A-kinase anchoring proteins (AKAPs), little attention has been paid to the charges involved in structure and function. To examine the electrostatic character of the structure of RIIalpha D/D we have predicted mean apparent pKa values, based on Poisson-Boltzmann electrostatic calculations, using an ensemble of calculated dimer structures. We propose that the helix promoting sequence Glu34-X-X-X-Arg38 stabilizes the second helix of each monomer, through the formation of a (i, i +4) side chain salt bridge. We show that a weak inter-helical hydrogen bond between Tyr35-Glu19 of each monomer contributes to tertiary packing and may be responsible for discriminating from alternative quaternary packing of the two monomers. We also show that an inter-monomer hydrogen bond between Asp30-Arg40 contributes to quaternary packing. We propose that the charged face comprising of Asp27-Asp30-Glu34-Arg38-Arg40-Glu41-Arg43-Arg44 may be necessary to provide flexibility or stability in the region between the C-terminus and the interdomain/autoinhibitory sequence of RIIalpha, depending on the activation state of PKA. We also discuss the structural requirements necessary for the formation of a stacked (rather than intertwined) dimer, which has consequences for the orientation of the functionally important and distinct faces.
-==About this Structure==
+Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha.,Morikis D, Roy M, Newlon MG, Scott JD, Jennings PA Eur J Biochem. 2002 Apr;269(8):2040-51. PMID:11985580<ref>PMID:11985580</ref>
-L6E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1L6E OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha., Morikis D, Roy M, Newlon MG, Scott JD, Jennings PA, Eur J Biochem. 2002 Apr;269(8):2040-51. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11985580 11985580]
+</div>
+<div class="pdbe-citations 1l6e" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Jennings PA]]
-[[Category: Single protein]]
+[[Category: Morikis D]]
-[[Category: Jennings, P.A.]]
+[[Category: Newlon MG]]
-[[Category: Morikis, D.]]
+[[Category: Roy M]]
-[[Category: Newlon, M.G.]]
+[[Category: Scott JD]]
-[[Category: Roy, M.]]
-[[Category: Scott, J.D.]]
-[[Category: anchoring]]
-[[Category: dimerization]]
-[[Category: docking]]
-[[Category: four-helix bundle]]
-[[Category: helix-loop-helix]]
-[[Category: regulatory subunit]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:18:49 2007''