7nqc: Difference between revisions
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==Calmodulin extracts the Ras family protein RalA from lipid bilayers by engagement with two membrane targeting motifs== | |||
<StructureSection load='7nqc' size='340' side='right'caption='[[7nqc]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7nqc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 30 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ULW:[(2~{Z},6~{Z})-3,7,11-trimethyldodeca-2,6-dienyl]+3-[2,5-bis(oxidanylidene)pyrrolidin-1-yl]propanoate'>ULW</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=7nqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nqc OCA], [https://pdbe.org/7nqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nqc RCSB], [https://www.ebi.ac.uk/pdbsum/7nqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nqc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CALM1_RAT CALM1_RAT] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2.[UniProtKB:P62158] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
RalA is a small GTPase and a member of the Ras family. This molecular switch is activated downstream of Ras and is widely implicated in tumor formation and growth. Previous work has shown that the ubiquitous Ca(2+)-sensor calmodulin (CaM) binds to small GTPases such as RalA and K-Ras4B, but a lack of structural information has obscured the functional consequences of these interactions. Here, we have investigated the binding of CaM to RalA and found that CaM interacts exclusively with the C terminus of RalA, which is lipidated with a prenyl group in vivo to aid membrane attachment. Biophysical and structural analyses show that the two RalA membrane-targeting motifs (the prenyl anchor and the polybasic motif) are engaged by distinct lobes of CaM and that CaM binding leads to removal of RalA from its membrane environment. The structure of this complex, along with a biophysical investigation into membrane removal, provides a framework with which to understand how CaM regulates the function of RalA and sheds light on the interaction of CaM with other small GTPases, including K-Ras4B. | |||
Calmodulin extracts the Ras family protein RalA from lipid bilayers by engagement with two membrane-targeting motifs.,Chamberlain SG, Gohlke A, Shafiq A, Squires IJ, Owen D, Mott HR Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104219118. doi: , 10.1073/pnas.2104219118. PMID:34480001<ref>PMID:34480001</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7nqc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Calmodulin 3D structures|Calmodulin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Chamberlain SG]] | |||
[[Category: Mott HR]] | |||
[[Category: Owen D]] | |||
Latest revision as of 16:46, 6 November 2024
Calmodulin extracts the Ras family protein RalA from lipid bilayers by engagement with two membrane targeting motifsCalmodulin extracts the Ras family protein RalA from lipid bilayers by engagement with two membrane targeting motifs
Structural highlights
FunctionCALM1_RAT Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2.[UniProtKB:P62158] Publication Abstract from PubMedRalA is a small GTPase and a member of the Ras family. This molecular switch is activated downstream of Ras and is widely implicated in tumor formation and growth. Previous work has shown that the ubiquitous Ca(2+)-sensor calmodulin (CaM) binds to small GTPases such as RalA and K-Ras4B, but a lack of structural information has obscured the functional consequences of these interactions. Here, we have investigated the binding of CaM to RalA and found that CaM interacts exclusively with the C terminus of RalA, which is lipidated with a prenyl group in vivo to aid membrane attachment. Biophysical and structural analyses show that the two RalA membrane-targeting motifs (the prenyl anchor and the polybasic motif) are engaged by distinct lobes of CaM and that CaM binding leads to removal of RalA from its membrane environment. The structure of this complex, along with a biophysical investigation into membrane removal, provides a framework with which to understand how CaM regulates the function of RalA and sheds light on the interaction of CaM with other small GTPases, including K-Ras4B. Calmodulin extracts the Ras family protein RalA from lipid bilayers by engagement with two membrane-targeting motifs.,Chamberlain SG, Gohlke A, Shafiq A, Squires IJ, Owen D, Mott HR Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104219118. doi: , 10.1073/pnas.2104219118. PMID:34480001[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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