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==Crystal Structure of the Rat Calcineurin== | |||
=== | <StructureSection load='4il1' size='340' side='right' caption='[[4il1]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4il1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IL1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IL1 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2r28|2r28]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Calm, Calm1, Calm2, Calm3, Calna, Cam, Cam1, Cam2, Cam3, Camb, Camc, Ppp3ca, Cna2, Cnb, Ppp3r1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=4il1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4il1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4il1 RCSB], [http://www.ebi.ac.uk/pdbsum/4il1 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Calcineurin is the only known calmodulin (CaM) activated protein phosphatase, which is involved in the regulation of numerous cellular and developmental processes and in calcium-dependent signal transduction. Although commonly assumed that CaM displaces the autoinhibitory domain (AID) blocking substrate access to its active site, the structural basis underlying activation remains elusive. We have created a fused ternary complex (CBA) by covalently linking three polypeptides: CaM, calcineurin regulatory B subunit (CnB) and calcineurin catalytic A subunit (CnA). CBA catalytic activity is comparable to that of fully activated native calcineurin in the presence of CaM. The crystal structure showed virtually no structural change in the active site and no evidence of CaM despite being covalently linked. The asymmetric unit contains four molecules; two parallel CBA pairs are packed in an antiparallel mode and the large cavities in crystal packing near the calcineurin active site would easily accommodate multiple positions of AID-bound CaM. Intriguingly, the conformation of the ordered segment of AID is not altered by CaM; thus, it is the disordered part of AID, which resumes a regular alpha-helical conformation upon binding to CaM, which is displaced by CaM for activation. We propose that the structural basis of calcineurin activation by CaM is through displacement of the disordered fragment of AID which otherwise impedes active site access. | |||
Structural basis of calcineurin activation by calmodulin.,Ye Q, Feng Y, Yin Y, Faucher F, Currie MA, Rahman MN, Jin J, Li S, Wei Q, Jia Z Cell Signal. 2013 Sep 7;25(12):2661-2667. doi: 10.1016/j.cellsig.2013.08.033. PMID:24018048<ref>PMID:24018048</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Phosphoprotein phosphatase]] | [[Category: Phosphoprotein phosphatase]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Faucher, F | [[Category: Faucher, F]] | ||
[[Category: Jia, Z | [[Category: Jia, Z]] | ||
[[Category: Ye, Q | [[Category: Ye, Q]] | ||
[[Category: Calcium-binding protein]] | [[Category: Calcium-binding protein]] | ||
[[Category: Chimera protein]] | [[Category: Chimera protein]] | ||
Revision as of 15:34, 21 December 2014
Crystal Structure of the Rat CalcineurinCrystal Structure of the Rat Calcineurin
Structural highlights
Publication Abstract from PubMedCalcineurin is the only known calmodulin (CaM) activated protein phosphatase, which is involved in the regulation of numerous cellular and developmental processes and in calcium-dependent signal transduction. Although commonly assumed that CaM displaces the autoinhibitory domain (AID) blocking substrate access to its active site, the structural basis underlying activation remains elusive. We have created a fused ternary complex (CBA) by covalently linking three polypeptides: CaM, calcineurin regulatory B subunit (CnB) and calcineurin catalytic A subunit (CnA). CBA catalytic activity is comparable to that of fully activated native calcineurin in the presence of CaM. The crystal structure showed virtually no structural change in the active site and no evidence of CaM despite being covalently linked. The asymmetric unit contains four molecules; two parallel CBA pairs are packed in an antiparallel mode and the large cavities in crystal packing near the calcineurin active site would easily accommodate multiple positions of AID-bound CaM. Intriguingly, the conformation of the ordered segment of AID is not altered by CaM; thus, it is the disordered part of AID, which resumes a regular alpha-helical conformation upon binding to CaM, which is displaced by CaM for activation. We propose that the structural basis of calcineurin activation by CaM is through displacement of the disordered fragment of AID which otherwise impedes active site access. Structural basis of calcineurin activation by calmodulin.,Ye Q, Feng Y, Yin Y, Faucher F, Currie MA, Rahman MN, Jin J, Li S, Wei Q, Jia Z Cell Signal. 2013 Sep 7;25(12):2661-2667. doi: 10.1016/j.cellsig.2013.08.033. PMID:24018048[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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