View source for 4aqr


==Crystal structure of calmodulin in complex with the regulatory domain of a plasma-membrane Ca2+-ATPase==
<StructureSection load='4aqr' size='340' side='right'caption='[[4aqr]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4aqr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AQR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</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></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=4aqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aqr OCA], [https://pdbe.org/4aqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aqr RCSB], [https://www.ebi.ac.uk/pdbsum/4aqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aqr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CALM7_ARATH CALM7_ARATH] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Activates MPK8 in vitro.<ref>PMID:21419340</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Calcium ions (Ca(2+)) have an important role as secondary messengers in numerous signal transduction processes, and cells invest much energy in controlling and maintaining a steep gradient between intracellular ( approximately 0.1-micromolar) and extracellular ( approximately 2-millimolar) Ca(2+) concentrations. Calmodulin-stimulated calcium pumps, which include the plasma-membrane Ca(2+)-ATPases (PMCAs), are key regulators of intracellular Ca(2+) in eukaryotes. They contain a unique amino- or carboxy-terminal regulatory domain responsible for autoinhibition, and binding of calcium-loaded calmodulin to this domain releases autoinhibition and activates the pump. However, the structural basis for the activation mechanism is unknown and a key remaining question is how calmodulin-mediated PMCA regulation can cover both basal Ca(2+) levels in the nanomolar range as well as micromolar-range Ca(2+) transients generated by cell stimulation. Here we present an integrated study combining the determination of the high-resolution crystal structure of a PMCA regulatory-domain/calmodulin complex with in vivo characterization and biochemical, biophysical and bioinformatics data that provide mechanistic insights into a two-step PMCA activation mechanism mediated by calcium-loaded calmodulin. The structure shows the entire PMCA regulatory domain and reveals an unexpected 2:1 stoichiometry with two calcium-loaded calmodulin molecules binding to different sites on a long helix. A multifaceted characterization of the role of both sites leads to a general structural model for calmodulin-mediated regulation of PMCAs that allows stringent, highly responsive control of intracellular calcium in eukaryotes, making it possible to maintain a stable, basal level at a threshold Ca(2+) concentration, where steep activation occurs.

A bimodular mechanism of calcium control in eukaryotes.,Tidow H, Poulsen LR, Andreeva A, Knudsen M, Hein KL, Wiuf C, Palmgren MG, Nissen P Nature. 2012 Oct 21. doi: 10.1038/nature11539. PMID:23086147<ref>PMID:23086147</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4aqr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arabidopsis thaliana]]
[[Category: Large Structures]]
[[Category: Andreeva A]]
[[Category: Hein KL]]
[[Category: Nissen P]]
[[Category: Palmgren MG]]
[[Category: Poulsen LR]]
[[Category: Tidow H]]