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| - | [[Image:3qf2.png|left|200px]] | + | ==Crystal structure of NALP3 PYD== |
| | + | <StructureSection load='3qf2' size='340' side='right' caption='[[3qf2]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[3qf2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QF2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QF2 FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NALP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> |
| | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qf2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qf2 RCSB], [http://www.ebi.ac.uk/pdbsum/3qf2 PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/NALP3_HUMAN NALP3_HUMAN]] Familial cold urticaria;CINCA syndrome with NLRP3 mutations;Muckle-Wells syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/NALP3_HUMAN NALP3_HUMAN]] May function as an inducer of apoptosis. Interacts selectively with ASC and this complex may function as an upstream activator of NF-kappa-B signaling. Inhibits TNF-alpha induced activation and nuclear translocation of RELA/NF-KB p65. Also inhibits transcriptional activity of RELA. Activates caspase-1 in response to a number of triggers including bacterial or viral infection which leads to processing and release of IL1B and IL18.<ref>PMID:11786556</ref> <ref>PMID:14662828</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | NALP3 inflammasome, composed of the three proteins NALP3, ASC, and Caspase-1, is a macromolecular complex responsible for the innate immune response against infection with bacterial and viral pathogens. Formation of the inflammasome can lead to the activation of inflammatory caspases, such as Caspase-1, which then activate pro-inflammatory cytokines by proteolytic cleavage. The assembly of the NALP3 inflammasome depends on the protein-interacting domain known as the death domain superfamily. NALP3 inflammasome is assembled via a pyrin domain (PYD)/PYD interaction between ASC and NALP3 and a caspase recruitment domain/caspase recruitment domain interaction between ASC and Caspase-1. As a first step toward elucidating the molecular mechanisms of inflammatory caspase activation by formation of inflammasome, we report the crystal structure of the PYD from NALP3 at 1.7-A resolution. Although NALP3 PYD has the canonical six-helical bundle structural fold similar to other PYDs, the high resolution structure reveals the possible biologically important homodimeric interface and the dynamic properties of the fold. Comparison with other PYD structures shows both similarities and differences that may be functionally relevant. Structural and sequence analyses further implicate conserved surface residues in NALP3 PYD for ASC interaction and inflammasome assembly. The most interesting aspect of the structure was the unexpected disulfide bond between Cys-8 and Cys-108, which might be important for regulation of the activity of NALP3 by redox potential. |
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| + | Crystal Structure of NALP3 Protein Pyrin Domain (PYD) and Its Implications in Inflammasome Assembly.,Bae JY, Park HH J Biol Chem. 2011 Nov 11;286(45):39528-36. Epub 2011 Aug 31. PMID:21880711<ref>PMID:21880711</ref> |
| - | The line below this paragraph, containing "STRUCTURE_3qf2", creates the "Structure Box" on the page.
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| - | {{STRUCTURE_3qf2| PDB=3qf2 | SCENE= }}
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| | | | |
| - | ===Crystal structure of NALP3 PYD===
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | | + | </div> |
| - | | + | == References == |
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| - | {{ABSTRACT_PUBMED_21880711}}
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| - | ==About this Structure==
| + | |
| - | [[3qf2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QF2 OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:021880711</ref><references group="xtra"/> | + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Bae, J Y.]] | | [[Category: Bae, J Y.]] |
| Structural highlights
3qf2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | NALP3 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[NALP3_HUMAN] Familial cold urticaria;CINCA syndrome with NLRP3 mutations;Muckle-Wells syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[NALP3_HUMAN] May function as an inducer of apoptosis. Interacts selectively with ASC and this complex may function as an upstream activator of NF-kappa-B signaling. Inhibits TNF-alpha induced activation and nuclear translocation of RELA/NF-KB p65. Also inhibits transcriptional activity of RELA. Activates caspase-1 in response to a number of triggers including bacterial or viral infection which leads to processing and release of IL1B and IL18.[1] [2]
Publication Abstract from PubMed
NALP3 inflammasome, composed of the three proteins NALP3, ASC, and Caspase-1, is a macromolecular complex responsible for the innate immune response against infection with bacterial and viral pathogens. Formation of the inflammasome can lead to the activation of inflammatory caspases, such as Caspase-1, which then activate pro-inflammatory cytokines by proteolytic cleavage. The assembly of the NALP3 inflammasome depends on the protein-interacting domain known as the death domain superfamily. NALP3 inflammasome is assembled via a pyrin domain (PYD)/PYD interaction between ASC and NALP3 and a caspase recruitment domain/caspase recruitment domain interaction between ASC and Caspase-1. As a first step toward elucidating the molecular mechanisms of inflammatory caspase activation by formation of inflammasome, we report the crystal structure of the PYD from NALP3 at 1.7-A resolution. Although NALP3 PYD has the canonical six-helical bundle structural fold similar to other PYDs, the high resolution structure reveals the possible biologically important homodimeric interface and the dynamic properties of the fold. Comparison with other PYD structures shows both similarities and differences that may be functionally relevant. Structural and sequence analyses further implicate conserved surface residues in NALP3 PYD for ASC interaction and inflammasome assembly. The most interesting aspect of the structure was the unexpected disulfide bond between Cys-8 and Cys-108, which might be important for regulation of the activity of NALP3 by redox potential.
Crystal Structure of NALP3 Protein Pyrin Domain (PYD) and Its Implications in Inflammasome Assembly.,Bae JY, Park HH J Biol Chem. 2011 Nov 11;286(45):39528-36. Epub 2011 Aug 31. PMID:21880711[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Manji GA, Wang L, Geddes BJ, Brown M, Merriam S, Al-Garawi A, Mak S, Lora JM, Briskin M, Jurman M, Cao J, DiStefano PS, Bertin J. PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B. J Biol Chem. 2002 Mar 29;277(13):11570-5. Epub 2002 Jan 10. PMID:11786556 doi:http://dx.doi.org/10.1074/jbc.M112208200
- ↑ O'Connor W Jr, Harton JA, Zhu X, Linhoff MW, Ting JP. Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-kappa B suppressive properties. J Immunol. 2003 Dec 15;171(12):6329-33. PMID:14662828
- ↑ Bae JY, Park HH. Crystal Structure of NALP3 Protein Pyrin Domain (PYD) and Its Implications in Inflammasome Assembly. J Biol Chem. 2011 Nov 11;286(45):39528-36. Epub 2011 Aug 31. PMID:21880711 doi:10.1074/jbc.M111.278812
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