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4ifp

From Proteopedia

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X-ray Crystal Structure of Human NLRP1 CARD Domain

Structural highlights

4ifp is a 3 chain structure with sequence from Escherichia coli K-12 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9948Å
Ligands:	, ,
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

MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.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

The NLRP1 inflammasome responds to microbial challenges such as Bacillus anthracis infection and is implicated in autoimmune disease such as vitiligo. Human NLRP1 contains both an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain (CARD), with the latter being essential for its association with the downstream effector procaspase-1. Here we report a 2.0 A crystal structure of the human NLRP1 CARD as a fusion with the maltose-binding protein. The structure reveals the six-helix bundle fold of the NLRP1 CARD, typical of the death domain superfamily. The charge surface of the NLRP1 CARD structure and a procaspase-1 CARD model suggests potential mechanisms for their association through electrostatic attraction. Proteins 2013. (c) 2013 Wiley Periodicals, Inc.

Structure of the NLRP1 caspase recruitment domain suggests potential mechanisms for its association with procaspase-1.,Jin T, Curry J, Smith P, Jiang J, Xiao TS Proteins. 2013 Mar 18. doi: 10.1002/prot.24287. PMID:23508996^[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
↑ Jin T, Curry J, Smith P, Jiang J, Xiao TS. Structure of the NLRP1 caspase recruitment domain suggests potential mechanisms for its association with procaspase-1. Proteins. 2013 Mar 18. doi: 10.1002/prot.24287. PMID:23508996 doi:10.1002/prot.24287

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ifp"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4ifp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IFP FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9948&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</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=4ifp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ifp OCA], [https://pdbe.org/4ifp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ifp RCSB], [https://www.ebi.ac.uk/pdbsum/4ifp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ifp ProSAT]</span></td></tr>
 </table>

4ifp

From Proteopedia

Current revision

X-ray Crystal Structure of Human NLRP1 CARD Domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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