6k7v

From Proteopedia

(Difference between revisions)

Revision as of 06:47, 24 March 2021

Structure of NLRP1 CARD filament

Structural highlights

6k7v is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NLRP1, CARD7, DEFCAP, KIAA0926, NAC, NALP1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[NLRP1_HUMAN] Vitiligo-associated autoimmune disease;Vitiligo;Corneal intraepithelial dyskeratosis with palmoplantar hyperkeratosis and laryngeal dyskeratosis. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry.

Function

[NLRP1_HUMAN] As the sensor component of the NLRP1 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP1, CASP1, and possibly PYCARD. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP1 inflammasome is also required for HMGB1 secretion. The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death (PubMed:22665479, PubMed:17418785). May be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561). Contrary to its mouse ortholog, not activated by Bacillus anthracis lethal toxin (PubMed:19651869). It is unclear whether isoform 2 is involved in inflammasome formation. It is not cleaved within the FIIND domain, does not assemble into specks, nor promote IL1B release (PubMed:22665479). However, in an vitro cell-free system, it has been shown to be activated by MDP (PubMed:17349957). Binds ATP (PubMed:11113115, PubMed:15212762).[UniProtKB:A1Z198]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIIND(UPA)-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIIND(UPA)-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIIND(UPA). Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells-a process that is greatly enhanced by NLRP1-FIIND(UPA) which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 A, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes.

Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8.,Gong Q, Robinson K, Xu C, Huynh PT, Chong KHC, Tan EYJ, Zhang J, Boo ZZ, Teo DET, Lay K, Zhang Y, Lim JSY, Goh WI, Wright G, Zhong FL, Reversade B, Wu B Nat Commun. 2021 Jan 8;12(1):188. doi: 10.1038/s41467-020-20319-5. PMID:33420028^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC. A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis. J Biol Chem. 2001 Mar 23;276(12):9239-45. doi: 10.1074/jbc.M006309200. Epub 2000 , Dec 11. PMID:11113115 doi:http://dx.doi.org/10.1074/jbc.M006309200
↑ Liu F, Lo CF, Ning X, Kajkowski EM, Jin M, Chiriac C, Gonzales C, Naureckiene S, Lock YW, Pong K, Zaleska MM, Jacobsen JS, Silverman S, Ozenberger BA. Expression of NALP1 in cerebellar granule neurons stimulates apoptosis. Cell Signal. 2004 Sep;16(9):1013-21. PMID:15212762 doi:10.1016/j.cellsig.2004.02.006
↑ Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E, Bailly-Maitre B, Volkmann N, Hanein D, Rouiller I, Reed JC. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell. 2007 Mar 9;25(5):713-24. PMID:17349957 doi:10.1016/j.molcel.2007.01.032
↑ Bruey JM, Bruey-Sedano N, Luciano F, Zhai D, Balpai R, Xu C, Kress CL, Bailly-Maitre B, Li X, Osterman A, Matsuzawa S, Terskikh AV, Faustin B, Reed JC. Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell. 2007 Apr 6;129(1):45-56. doi: 10.1016/j.cell.2007.01.045. PMID:17418785 doi:http://dx.doi.org/10.1016/j.cell.2007.01.045
↑ Hsu LC, Ali SR, McGillivray S, Tseng PH, Mariathasan S, Humke EW, Eckmann L, Powell JJ, Nizet V, Dixit VM, Karin M. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7803-8. doi:, 10.1073/pnas.0802726105. Epub 2008 May 29. PMID:18511561 doi:http://dx.doi.org/10.1073/pnas.0802726105
↑ Liao KC, Mogridge J. Expression of Nlrp1b inflammasome components in human fibroblasts confers susceptibility to anthrax lethal toxin. Infect Immun. 2009 Oct;77(10):4455-62. doi: 10.1128/IAI.00276-09. Epub 2009 Aug, 3. PMID:19651869 doi:http://dx.doi.org/10.1128/IAI.00276-09
↑ Finger JN, Lich JD, Dare LC, Cook MN, Brown KK, Duraiswami C, Bertin J, Gough PJ. Autolytic proteolysis within the function to find domain (FIIND) is required for NLRP1 inflammasome activity. J Biol Chem. 2012 Jul 20;287(30):25030-7. doi: 10.1074/jbc.M112.378323. Epub 2012, Jun 4. PMID:22665479 doi:http://dx.doi.org/10.1074/jbc.M112.378323
↑ Zhong FL, Mamai O, Sborgi L, Boussofara L, Hopkins R, Robinson K, Szeverenyi I, Takeichi T, Balaji R, Lau A, Tye H, Roy K, Bonnard C, Ahl PJ, Jones LA, Baker PJ, Lacina L, Otsuka A, Fournie PR, Malecaze F, Lane EB, Akiyama M, Kabashima K, Connolly JE, Masters SL, Soler VJ, Omar SS, McGrath JA, Nedelcu R, Gribaa M, Denguezli M, Saad A, Hiller S, Reversade B. Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation. Cell. 2016 Sep 22;167(1):187-202.e17. doi: 10.1016/j.cell.2016.09.001. PMID:27662089 doi:http://dx.doi.org/10.1016/j.cell.2016.09.001
↑ Gong Q, Robinson K, Xu C, Huynh PT, Chong KHC, Tan EYJ, Zhang J, Boo ZZ, Teo DET, Lay K, Zhang Y, Lim JSY, Goh WI, Wright G, Zhong FL, Reversade B, Wu B. Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8. Nat Commun. 2021 Jan 8;12(1):188. doi: 10.1038/s41467-020-20319-5. PMID:33420028 doi:http://dx.doi.org/10.1038/s41467-020-20319-5

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6k7v"

@@ Line 1: / Line 1: @@
 ==Structure of NLRP1 CARD filament==
-<StructureSection load='6k7v' size='340' side='right'caption='[[6k7v]]' scene=''>
+<StructureSection load='6k7v' size='340' side='right'caption='[[6k7v]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K7V OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6K7V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6k7v]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K7V FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6k7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k7v OCA], [http://pdbe.org/6k7v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6k7v RCSB], [http://www.ebi.ac.uk/pdbsum/6k7v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6k7v ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NLRP1, CARD7, DEFCAP, KIAA0926, NAC, NALP1 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6k7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k7v OCA], [https://pdbe.org/6k7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k7v RCSB], [https://www.ebi.ac.uk/pdbsum/6k7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k7v ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[[https://www.uniprot.org/uniprot/NLRP1_HUMAN NLRP1_HUMAN]] Vitiligo-associated autoimmune disease;Vitiligo;Corneal intraepithelial dyskeratosis with palmoplantar hyperkeratosis and laryngeal dyskeratosis. Disease susceptibility is associated with variations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease may be caused by mutations affecting the gene represented in this entry.
+== Function ==
+[[https://www.uniprot.org/uniprot/NLRP1_HUMAN NLRP1_HUMAN]] As the sensor component of the NLRP1 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP1, CASP1, and possibly PYCARD. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP1 inflammasome is also required for HMGB1 secretion. The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death (PubMed:22665479, PubMed:17418785). May be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561). Contrary to its mouse ortholog, not activated by Bacillus anthracis lethal toxin (PubMed:19651869). It is unclear whether isoform 2 is involved in inflammasome formation. It is not cleaved within the FIIND domain, does not assemble into specks, nor promote IL1B release (PubMed:22665479). However, in an vitro cell-free system, it has been shown to be activated by MDP (PubMed:17349957). Binds ATP (PubMed:11113115, PubMed:15212762).[UniProtKB:A1Z198]<ref>PMID:11113115</ref> <ref>PMID:15212762</ref> <ref>PMID:17349957</ref> <ref>PMID:17418785</ref> <ref>PMID:18511561</ref> <ref>PMID:19651869</ref> <ref>PMID:22665479</ref> <ref>PMID:27662089</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIIND(UPA)-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIIND(UPA)-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIIND(UPA). Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells-a process that is greatly enhanced by NLRP1-FIIND(UPA) which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 A, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes.
+Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8.,Gong Q, Robinson K, Xu C, Huynh PT, Chong KHC, Tan EYJ, Zhang J, Boo ZZ, Teo DET, Lay K, Zhang Y, Lim JSY, Goh WI, Wright G, Zhong FL, Reversade B, Wu B Nat Commun. 2021 Jan 8;12(1):188. doi: 10.1038/s41467-020-20319-5. PMID:33420028<ref>PMID:33420028</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6k7v" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Bin W]]
+[[Category: Gong, Q]]
-[[Category: Chenrui X]]
+[[Category: Wu, B]]
-[[Category: Jiawen Z]]
+[[Category: Xu, C]]
-[[Category: Qin G]]
+[[Category: Zhang, J]]
+[[Category: Filament]]
+[[Category: Signaling protein]]

6k7v

From Proteopedia

Revision as of 06:47, 24 March 2021

Structure of NLRP1 CARD filament

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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