2lg1

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<StructureSection load='2lg1' size='340' side='right' caption='[[2lg1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='2lg1' size='340' side='right' caption='[[2lg1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2lg1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LG1 OCA]. <br>
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<table><tr><td colspan='2'>[[2lg1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LG1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LG1 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKAP13, BRX, HT31, LBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKAP13, BRX, HT31, LBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lg1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lg1 RCSB], [http://www.ebi.ac.uk/pdbsum/2lg1 PDBsum]</span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lg1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lg1 RCSB], [http://www.ebi.ac.uk/pdbsum/2lg1 PDBsum]</span></td></tr>
<table>
<table>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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The human AKAP13 protein contains DH and PH domains, which are responsible for its cell transforming activity. Despite its biomedical importance, the contribution of the PH domain to AKAP13 activity remains unclear and no three dimensional structure is available to date. Here we report the backbone and side chain (1)H, (13)C and (15)N resonance assignments of a 20 kDa construct comprising the uniformly (13)C and( 15)N labeled AKAP13-PH domain and an associated helix from the DH domain which is required for its stable expression. Resonance assignment has been achieved using conventional triple resonance experiments; 95% of all back bone resonances and more than 90% of side chain resonances have been successfully assigned. The (1)H, (13)C and (15)N chemical shifts have been deposited in BMRB with accession number of 16195.
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The small GTPase RhoA promotes deregulated signalling upon interaction with Lbc, the oncogenic form of A-kinase anchoring protein (AKAP). The onco-Lbc protein is a hyperactive Rho-specific guanine nucleotide exchange factor (GEF), but its structural mechanism has not been reported, despite its involvement in cardiac hypertrophy and cancer causation. The pleckstrin homology (PH) domain of Lbc is located at the C-terminal end of the protein, and is shown here to specifically recognize activated RhoA rather than lipids. The isolated dbl homology (DH) domain can function as an independent activator with an enhanced activity. However, the DH domain normally does not act as a solitary Lbc interface with RhoA-GDP. Instead it is negatively controlled by the PH domain. In particular the DH helical bundle is coupled to the structurally dependent PH domain through a helical linker, which reduces its activity. Together the two domains form a rigid scaffold in solution, as evidenced by small angle X-ray scattering and 1H,13C,15N-based NMR spectroscopy. The two domains assume a "chair" shape, with its back possessing independent GEF activity, and the PH domain providing a broad seat for RhoA-GTP docking rather than membrane recognition. This provides structural and dynamical insights into how DH and PH domains work together in solution to support regulated RhoA activity. Mutational analysis supports the bifunctional PH domain mediation of DH:RhoA interactions and explains why the tandem domain is required for controlled GEF signaling.
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Resonance assignments of the human AKAP13-PH domain and stabilizing DH helix.,Sugawara M, Whittaker SB, Bishop S, Ball L, Overduin M Biomol NMR Assign. 2009 Dec;3(2):215-8. Epub 2009 Jul 18. PMID:19888694<ref>PMID:19888694</ref>
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Structural Insights into the Activation of the RhoA GTPase by the Lbc Oncoprotein.,Lenoir M, Sugawara M, Kaur J, Ball LJ, Overduin M J Biol Chem. 2014 Jul 3. pii: jbc.M114.561787. PMID:24993829<ref>PMID:24993829</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
== References ==
== References ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Human]]
[[Category: Ball, L.]]
[[Category: Ball, L.]]
[[Category: Lenoir, M.]]
[[Category: Lenoir, M.]]

Revision as of 06:34, 13 August 2014

Solution structure of the human AKAP13 PH domain and stabilizing DH helix

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