|
|
| (13 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:2nsn.gif|left|200px]]<br /> | |
| - | <applet load="2nsn" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2nsn, resolution 2.000Å" /> | |
| - | '''Crystal structure of Caspace Activation and Recruitment Domain (CARD) of NOD1'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Crystal structure of Caspace Activation and Recruitment Domain (CARD) of NOD1== |
| - | Nod-like receptors (NLRs), Nod1 and Nod2 are cytosolic detectors of, pathogen-associated molecular patterns (PAMPs). Nod1 is a three-domain, protein, consisting of a caspase activation and recruitment domain (CARD), a nucleotide-binding oligomerization domain (NOD), and a leucine-rich, repeat domain (LRR). The binding of PAMPs to the LRR results in the, activation of signaling through homophilic CARD-CARD interactions. Several, CARD structures have been determined, including a recent NMR structure of, Nod1 CARD. In contrast to the reported NMR structure, the crystal, structure reported here is a dimer, where the sixth helix is swapped, between two monomers. While the overall structure is very similar to the, known CARD structures, this is the first report of a homodimeric CARD, structure. The ability of the CARD to exist in monomeric and dimeric forms, suggests another level of regulation in the activation of NLR proteins. | + | <StructureSection load='2nsn' size='340' side='right'caption='[[2nsn]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2nsn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NSN FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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=2nsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nsn OCA], [https://pdbe.org/2nsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nsn RCSB], [https://www.ebi.ac.uk/pdbsum/2nsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nsn ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NOD1_HUMAN NOD1_HUMAN] Enhances caspase-9-mediated apoptosis. Induces NF-kappa-B activity via RIPK2 and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS). Forms an intracellular sensing system along with ARHGEF2 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIPK2 dependent NF-kappa-B signaling pathway activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides but also in the activation of NF-kappa-B by Shigella effector proteins IpgB2 and OspB. Recruits NLRP10 to the cell membrane following bacterial infection.<ref>PMID:11058605</ref> <ref>PMID:19043560</ref> <ref>PMID:22672233</ref> <ref>PMID:17054981</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Nod-like receptors (NLRs), Nod1 and Nod2 are cytosolic detectors of pathogen-associated molecular patterns (PAMPs). Nod1 is a three-domain protein, consisting of a caspase activation and recruitment domain (CARD), a nucleotide-binding oligomerization domain (NOD), and a leucine-rich repeat domain (LRR). The binding of PAMPs to the LRR results in the activation of signaling through homophilic CARD-CARD interactions. Several CARD structures have been determined, including a recent NMR structure of Nod1 CARD. In contrast to the reported NMR structure, the crystal structure reported here is a dimer, where the sixth helix is swapped between two monomers. While the overall structure is very similar to the known CARD structures, this is the first report of a homodimeric CARD structure. The ability of the CARD to exist in monomeric and dimeric forms suggests another level of regulation in the activation of NLR proteins. |
| | | | |
| - | ==Disease==
| + | Crystal structure of the Nod1 caspase activation and recruitment domain.,Coussens NP, Mowers JC, McDonald C, Nunez G, Ramaswamy S Biochem Biophys Res Commun. 2007 Feb 2;353(1):1-5. Epub 2006 Dec 6. PMID:17173864<ref>PMID:17173864</ref> |
| - | Known disease associated with this structure: Hydatidiform mole OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609661 609661]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 2NSN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2NSN OCA].
| + | </div> |
| - | | + | <div class="pdbe-citations 2nsn" style="background-color:#fffaf0;"></div> |
| - | ==Reference== | + | == References == |
| - | Crystal structure of the Nod1 caspase activation and recruitment domain., Coussens NP, Mowers JC, McDonald C, Nunez G, Ramaswamy S, Biochem Biophys Res Commun. 2007 Feb 2;353(1):1-5. Epub 2006 Dec 6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17173864 17173864]
| + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Coussens, N.P.]] | + | [[Category: Coussens NP]] |
| - | [[Category: Ramaswamy, S.]] | + | [[Category: Ramaswamy S]] |
| - | [[Category: six helix greek key motif]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:02:20 2007''
| + | |
| Structural highlights
Function
NOD1_HUMAN Enhances caspase-9-mediated apoptosis. Induces NF-kappa-B activity via RIPK2 and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS). Forms an intracellular sensing system along with ARHGEF2 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIPK2 dependent NF-kappa-B signaling pathway activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides but also in the activation of NF-kappa-B by Shigella effector proteins IpgB2 and OspB. Recruits NLRP10 to the cell membrane following bacterial infection.[1] [2] [3] [4]
Publication Abstract from PubMed
Nod-like receptors (NLRs), Nod1 and Nod2 are cytosolic detectors of pathogen-associated molecular patterns (PAMPs). Nod1 is a three-domain protein, consisting of a caspase activation and recruitment domain (CARD), a nucleotide-binding oligomerization domain (NOD), and a leucine-rich repeat domain (LRR). The binding of PAMPs to the LRR results in the activation of signaling through homophilic CARD-CARD interactions. Several CARD structures have been determined, including a recent NMR structure of Nod1 CARD. In contrast to the reported NMR structure, the crystal structure reported here is a dimer, where the sixth helix is swapped between two monomers. While the overall structure is very similar to the known CARD structures, this is the first report of a homodimeric CARD structure. The ability of the CARD to exist in monomeric and dimeric forms suggests another level of regulation in the activation of NLR proteins.
Crystal structure of the Nod1 caspase activation and recruitment domain.,Coussens NP, Mowers JC, McDonald C, Nunez G, Ramaswamy S Biochem Biophys Res Commun. 2007 Feb 2;353(1):1-5. Epub 2006 Dec 6. PMID:17173864[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Inohara N, Ogura Y, Chen FF, Muto A, Nunez G. Human Nod1 confers responsiveness to bacterial lipopolysaccharides. J Biol Chem. 2001 Jan 26;276(4):2551-4. Epub 2000 Oct 31. PMID:11058605 doi:10.1074/jbc.M009728200
- ↑ Fukazawa A, Alonso C, Kurachi K, Gupta S, Lesser CF, McCormick BA, Reinecker HC. GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. PLoS Pathog. 2008 Nov;4(11):e1000228. doi: 10.1371/journal.ppat.1000228. Epub, 2008 Nov 28. PMID:19043560 doi:10.1371/journal.ppat.1000228
- ↑ Lautz K, Damm A, Menning M, Wenger J, Adam AC, Zigrino P, Kremmer E, Kufer TA. NLRP10 enhances Shigella-induced pro-inflammatory responses. Cell Microbiol. 2012 Oct;14(10):1568-83. doi: 10.1111/j.1462-5822.2012.01822.x., Epub 2012 Jun 21. PMID:22672233 doi:10.1111/j.1462-5822.2012.01822.x
- ↑ Manon F, Favier A, Nunez G, Simorre JP, Cusack S. Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK. J Mol Biol. 2007 Jan 5;365(1):160-74. Epub 2006 Sep 29. PMID:17054981 doi:10.1016/j.jmb.2006.09.067
- ↑ Coussens NP, Mowers JC, McDonald C, Nunez G, Ramaswamy S. Crystal structure of the Nod1 caspase activation and recruitment domain. Biochem Biophys Res Commun. 2007 Feb 2;353(1):1-5. Epub 2006 Dec 6. PMID:17173864 doi:S0006-291X(06)02513-7
|
