4ora: Difference between revisions
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<StructureSection load='4ora' size='340' side='right'caption='[[4ora]], [[Resolution|resolution]] 2.75Å' scene=''> | <StructureSection load='4ora' size='340' side='right'caption='[[4ora]], [[Resolution|resolution]] 2.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ora]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4ora]] 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=4ORA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ORA 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>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </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=FE:FE+(III)+ION'>FE</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=4ora FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ora OCA], [https://pdbe.org/4ora PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ora RCSB], [https://www.ebi.ac.uk/pdbsum/4ora PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ora ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PP2BB_HUMAN PP2BB_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Ca(2+)/calmodulin-dependent protein phosphatase calcineurin (CN), a heterodimer composed of a catalytic subunit A and an essential regulatory subunit B, plays critical functions in various cellular processes such as cardiac hypertrophy and T cell activation. It is the target of the most widely used immunosuppressants for transplantation, tacrolimus (FK506) and cyclosporin A. However, the structure of a large part of the CNA regulatory region remains to be determined, and there has been considerable debate concerning the regulation of CN activity. Here, we report the crystal structure of full-length CN (beta isoform), which revealed a novel autoinhibitory segment (AIS) in addition to the well-known autoinhibitory domain (AID). The AIS nestles in a hydrophobic intersubunit groove, which overlaps the recognition site for substrates and immunosuppressant-immunophilin complexes. Indeed, disruption of this AIS interaction results in partial stimulation of CN activity. More importantly, our biochemical studies demonstrate that calmodulin does not remove AID from the active site, but only regulates the orientation of AID with respect to the catalytic core, causing incomplete activation of CN. Our findings challenge the current model for CN activation, and provide a better understanding of molecular mechanisms of CN activity regulation. | |||
Cooperative autoinhibition and multi-level activation mechanisms of calcineurin.,Li SJ, Wang J, Ma L, Lu C, Wang J, Wu JW, Wang ZX Cell Res. 2016 Mar;26(3):336-49. doi: 10.1038/cr.2016.14. Epub 2016 Jan 22. PMID:26794871<ref>PMID:26794871</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ora" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Calcineurin|Calcineurin]] | *[[Calcineurin 3D structures|Calcineurin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Li SJ]] | |||
[[Category: Li | [[Category: Wang J]] | ||
[[Category: Wang | [[Category: Wang ZX]] | ||
[[Category: Wang | [[Category: Wu JW]] | ||
[[Category: Wu | |||
Revision as of 10:42, 25 January 2023
Crystal structure of a human calcineurin mutantCrystal structure of a human calcineurin mutant
Structural highlights
FunctionPP2BB_HUMAN Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Publication Abstract from PubMedThe Ca(2+)/calmodulin-dependent protein phosphatase calcineurin (CN), a heterodimer composed of a catalytic subunit A and an essential regulatory subunit B, plays critical functions in various cellular processes such as cardiac hypertrophy and T cell activation. It is the target of the most widely used immunosuppressants for transplantation, tacrolimus (FK506) and cyclosporin A. However, the structure of a large part of the CNA regulatory region remains to be determined, and there has been considerable debate concerning the regulation of CN activity. Here, we report the crystal structure of full-length CN (beta isoform), which revealed a novel autoinhibitory segment (AIS) in addition to the well-known autoinhibitory domain (AID). The AIS nestles in a hydrophobic intersubunit groove, which overlaps the recognition site for substrates and immunosuppressant-immunophilin complexes. Indeed, disruption of this AIS interaction results in partial stimulation of CN activity. More importantly, our biochemical studies demonstrate that calmodulin does not remove AID from the active site, but only regulates the orientation of AID with respect to the catalytic core, causing incomplete activation of CN. Our findings challenge the current model for CN activation, and provide a better understanding of molecular mechanisms of CN activity regulation. Cooperative autoinhibition and multi-level activation mechanisms of calcineurin.,Li SJ, Wang J, Ma L, Lu C, Wang J, Wu JW, Wang ZX Cell Res. 2016 Mar;26(3):336-49. doi: 10.1038/cr.2016.14. Epub 2016 Jan 22. PMID:26794871[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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