6n2p: Difference between revisions
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<StructureSection load='6n2p' size='340' side='right'caption='[[6n2p]], [[Resolution|resolution]] 4.00Å' scene=''> | <StructureSection load='6n2p' size='340' side='right'caption='[[6n2p]], [[Resolution|resolution]] 4.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6n2p]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N2P FirstGlance]. <br> | <table><tr><td colspan='2'>[[6n2p]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N2P FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6n2m|6n2m]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6n2m|6n2m]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CARD9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6n2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n2p OCA], [http://pdbe.org/6n2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n2p RCSB], [http://www.ebi.ac.uk/pdbsum/6n2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n2p ProSAT]</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=6n2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n2p OCA], [http://pdbe.org/6n2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n2p RCSB], [http://www.ebi.ac.uk/pdbsum/6n2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n2p ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/CARD9_HUMAN CARD9_HUMAN]] Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells.<ref>PMID:11053425</ref> | [[http://www.uniprot.org/uniprot/CARD9_HUMAN CARD9_HUMAN]] Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells.<ref>PMID:11053425</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CARD9 and CARD11 drive immune cell activation by nucleating Bcl10 polymerization, but are held in an autoinhibited state prior to stimulation. Here, we elucidate the structural basis for this autoinhibition by determining the structure of a region of CARD9 that includes an extensive interface between its caspase recruitment domain (CARD) and coiled-coil domain. We demonstrate, for both CARD9 and CARD11, that disruption of this interface leads to hyperactivation in cells and to the formation of Bcl10-templating filaments in vitro, illuminating the mechanism of action of numerous oncogenic mutations of CARD11. These structural insights enable us to characterize two similar, yet distinct, mechanisms by which autoinhibition is relieved in the course of canonical CARD9 or CARD11 activation. We also dissect the molecular determinants of helical template assembly by solving the structure of the CARD9 filament. Taken together, these findings delineate the structural mechanisms of inhibition and activation within this protein family. | |||
Structures of autoinhibited and polymerized forms of CARD9 reveal mechanisms of CARD9 and CARD11 activation.,Holliday MJ, Witt A, Rodriguez Gama A, Walters BT, Arthur CP, Halfmann R, Rohou A, Dueber EC, Fairbrother WJ Nat Commun. 2019 Jul 11;10(1):3070. doi: 10.1038/s41467-019-10953-z. PMID:31296852<ref>PMID:31296852</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6n2p" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Arthur, C P]] | [[Category: Arthur, C P]] | ||