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| | ==Crystal structure of Cell Inhibiting Factor (Cif) from Photorhabdus luminescens== | | ==Crystal structure of Cell Inhibiting Factor (Cif) from Photorhabdus luminescens== |
| - | <StructureSection load='3gqj' size='340' side='right' caption='[[3gqj]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='3gqj' size='340' side='right'caption='[[3gqj]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gqj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ccm_7076 Ccm 7076]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GQJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gqj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Photorhabdus_laumondii_subsp._laumondii Photorhabdus laumondii subsp. laumondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GQJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gqm|3gqm]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">plu2515 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=141679 CCM 7076])</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=3gqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gqj OCA], [https://pdbe.org/3gqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gqj RCSB], [https://www.ebi.ac.uk/pdbsum/3gqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gqj 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=3gqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gqj OCA], [http://pdbe.org/3gqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gqj RCSB], [http://www.ebi.ac.uk/pdbsum/3gqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gqj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/CIF_PHOLL CIF_PHOLL] Protein-glutamine deamidase effector that inhibits the host cell cycle and other key cellular processes such as the actin network and programmed-cell death (PubMed:19308257, PubMed:19225106, PubMed:20870031). Acts by mediating the side chain deamidation of 'Gln-40' of host NEDD8, converting it to glutamate, thereby abolishing the activity of cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (By similarity). Inactivation of CRL complexes prevents ubiquitination and subsequent degradation of the cyclin-dependent kinase inhibitors CDKN1A/p21 and CDKN1B/p27, leading to G1 and G2 cell cycle arrests in host cells (PubMed:19308257). Deamidation of 'Gln-40' of host NEDD8 also triggers macrophage-specific programmed cell death (By similarity). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (By similarity).[UniProtKB:Q63KH5]<ref>PMID:19225106</ref> <ref>PMID:19308257</ref> <ref>PMID:20870031</ref> |
| - | A pre-requisite for bacterial pathogenesis is the successful interaction of a pathogen with a host. One mechanism used by a broad range of Gram negative bacterial pathogens is to deliver effector proteins directly into host cells through a dedicated type III secretion system where they modulate host cell function. The cycle inhibiting factor (Cif) family of effector proteins, identified in a growing number of pathogens that harbour functional type III secretion systems and have a wide host range, arrest the eukaryotic cell cycle. Here, the crystal structures of Cifs from the insect pathogen/nematode symbiont Photorhabdus luminescens (a gamma-proteobacterium) and human pathogen Burkholderia pseudomallei (a beta-proteobacterium) are presented. Both of these proteins adopt an overall fold similar to the papain sub-family of cysteine proteases, as originally identified in the structure of a truncated form of Cif from Enteropathogenic E. coli (EPEC), despite sharing only limited sequence identity. The structure of an N-terminal region, referred to here as the 'tail-domain' (absent in the EPEC Cif structure), suggests a surface likely to be involved in host-cell substrate recognition. The conformation of the Cys-His-Gln catalytic triad is retained, and the essential cysteine is exposed to solvent and addressable by small molecule reagents. These structures and biochemical work contribute to the rapidly expanding literature on Cifs, and direct further studies to better understand the molecular details of the activity of these proteins.
| + | |
| - | | + | |
| - | Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.,Crow A, Race PR, Jubelin G, Varela Chavez C, Escoubas JM, Oswald E, Banfield MJ PLoS ONE. 2009;4(5):e5582. Epub 2009 May 18. PMID:19440549<ref>PMID:19440549</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 3gqj" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ccm 7076]] | + | [[Category: Large Structures]] |
| - | [[Category: Banfield, M J]] | + | [[Category: Photorhabdus laumondii subsp. laumondii]] |
| - | [[Category: Crow, A]] | + | [[Category: Banfield MJ]] |
| - | [[Category: Cell inhibiting factor]] | + | [[Category: Crow A]] |
| - | [[Category: Cif]]
| + | |
| - | [[Category: Protease-like]]
| + | |
| - | [[Category: Unknown function]]
| + | |
| Structural highlights
Function
CIF_PHOLL Protein-glutamine deamidase effector that inhibits the host cell cycle and other key cellular processes such as the actin network and programmed-cell death (PubMed:19308257, PubMed:19225106, PubMed:20870031). Acts by mediating the side chain deamidation of 'Gln-40' of host NEDD8, converting it to glutamate, thereby abolishing the activity of cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (By similarity). Inactivation of CRL complexes prevents ubiquitination and subsequent degradation of the cyclin-dependent kinase inhibitors CDKN1A/p21 and CDKN1B/p27, leading to G1 and G2 cell cycle arrests in host cells (PubMed:19308257). Deamidation of 'Gln-40' of host NEDD8 also triggers macrophage-specific programmed cell death (By similarity). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (By similarity).[UniProtKB:Q63KH5][1] [2] [3]
References
- ↑ Yao Q, Cui J, Zhu Y, Wang G, Hu L, Long C, Cao R, Liu X, Huang N, Chen S, Liu L, Shao F. A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3716-21. Epub 2009 Feb 18. PMID:19225106
- ↑ Jubelin G, Chavez CV, Taieb F, Banfield MJ, Samba-Louaka A, Nobe R, Nougayrede JP, Zumbihl R, Givaudan A, Escoubas JM, Oswald E. Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens. PLoS One. 2009;4(3):e4855. doi: 10.1371/journal.pone.0004855. Epub 2009 Mar 24. PMID:19308257 doi:http://dx.doi.org/10.1371/journal.pone.0004855
- ↑ Chavez CV, Jubelin G, Courties G, Gomard A, Ginibre N, Pages S, Taieb F, Girard PA, Oswald E, Givaudan A, Zumbihl R, Escoubas JM. The cyclomodulin Cif of Photorhabdus luminescens inhibits insect cell proliferation and triggers host cell death by apoptosis. Microbes Infect. 2010 Dec;12(14-15):1208-18. doi: 10.1016/j.micinf.2010.09.006., Epub 2010 Sep 24. PMID:20870031 doi:http://dx.doi.org/10.1016/j.micinf.2010.09.006
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