2mpc
From Proteopedia
(Difference between revisions)
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<StructureSection load='2mpc' size='340' side='right'caption='[[2mpc]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | <StructureSection load='2mpc' size='340' side='right'caption='[[2mpc]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2mpc]] is a 1 chain structure | + | <table><tr><td colspan='2'>[[2mpc]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MPC FirstGlance]. <br> |
| - | </td></tr> | + | </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=2mpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mpc OCA], [https://pdbe.org/2mpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mpc RCSB], [https://www.ebi.ac.uk/pdbsum/2mpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mpc ProSAT]</span></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=2mpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mpc OCA], [https://pdbe.org/2mpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mpc RCSB], [https://www.ebi.ac.uk/pdbsum/2mpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mpc ProSAT]</span></td></tr> | + | |
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/MEFV_HUMAN MEFV_HUMAN]] Probably controls the inflammatory response in myelomonocytic cells at the level of the cytoskeleton organization.<ref>PMID:10807793</ref> <ref>PMID:11468188</ref> | [[https://www.uniprot.org/uniprot/MEFV_HUMAN MEFV_HUMAN]] Probably controls the inflammatory response in myelomonocytic cells at the level of the cytoskeleton organization.<ref>PMID:10807793</ref> <ref>PMID:11468188</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Inflammasomes are macromolecular complexes that mediate inflammatory and cell death responses to pathogens and cellular stress signals. Dysregulated inflammasome activation is associated with autoinflammatory syndromes and several common diseases. During inflammasome assembly, oligomerized cytosolic pattern recognition receptors recruit procaspase-1 and procaspase-8 via the adaptor protein ASC. Inflammasome assembly is mediated by pyrin domains (PYDs) and caspase recruitment domains, which are protein interaction domains of the death fold superfamily. However, the molecular details of their interactions are poorly understood. We have studied the interaction between ASC and pyrin PYDs that mediates ASC recruitment to the pyrin inflammasome, which is implicated in the pathogenesis of familial Mediterranean fever. We demonstrate that both the ASC and pyrin PYDs have multifaceted binding modes, involving three sites on pyrin PYD and two sites on ASC PYD. Molecular docking of pyrin-ASC PYD complexes showed that pyrin PYD can simultaneously interact with up to three ASC PYDs. Furthermore, ASC PYD can self-associate and interact with pyrin, consistent with previous reports that pyrin promotes ASC clustering to form a proinflammatory complex. Finally, the effects of familial Mediterranean fever-associated mutations, R42W and A89T, on structural and functional properties of pyrin PYD were investigated. The R42W mutation had a significant effect on structure and increased stability. Although the R42W mutant exhibited reduced interaction with ASC, it also bound less to the pyrin B-box domain responsible for autoinhibition and hence may be constitutively active. Our data give new insights into the binding modes of PYDs and inflammasome architecture. | ||
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| + | Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly.,Vajjhala PR, Kaiser S, Smith SJ, Ong QR, Soh SL, Stacey KJ, Hill JM J Biol Chem. 2014 Aug 22;289(34):23504-19. doi: 10.1074/jbc.M114.553305. Epub, 2014 Jul 8. PMID:25006247<ref>PMID:25006247</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2mpc" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hill, J M]] | [[Category: Hill, J M]] | ||
Revision as of 04:55, 25 August 2022
Solution structure of the pyrin domain of human Pyrin
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