View source for 6uuq


==Structure of Calcineurin bound to RCAN1==
<StructureSection load='6uuq' size='340' side='right'caption='[[6uuq]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uuq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UUQ 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]] 1.849&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6uuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uuq OCA], [https://pdbe.org/6uuq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uuq RCSB], [https://www.ebi.ac.uk/pdbsum/6uuq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uuq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PP2BA_HUMAN PP2BA_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.<ref>PMID:15671020</ref> <ref>PMID:18838687</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Regulator of calcineurin 1 (RCAN1) is an endogenous inhibitor of the Ser/Thr phosphatase calcineurin (CN). It has been shown that excessive inhibition of CN is a critical factor for Down syndrome and Alzheimer's disease. Here, we determined RCAN1's mode of action. Using a combination of structural, biophysical, and biochemical studies, we show that RCAN1 inhibits CN via multiple routes: first, by blocking essential substrate recruitment sites and, second, by blocking the CN active site using two distinct mechanisms. We also show that phosphorylation either inhibits RCAN1-CN assembly or converts RCAN1 into a weak inhibitor, which can be reversed by CN via dephosphorylation. This highlights the interplay between posttranslational modifications in regulating CN activity. Last, this work advances our understanding of how active site inhibition of CN can be achieved in a highly specific manner. Together, these data provide the necessary road map for targeting multiple neurological disorders.

The structure of the RCAN1:CN complex explains the inhibition of and substrate recruitment by calcineurin.,Li Y, Sheftic SR, Grigoriu S, Schwieters CD, Page R, Peti W Sci Adv. 2020 Jul 1;6(27). pii: 6/27/eaba3681. doi: 10.1126/sciadv.aba3681. Print, 2020 Jul. PMID:32936779<ref>PMID:32936779</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6uuq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Page R]]
[[Category: Peti W]]
[[Category: Sheftic S]]