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| | ==Structure of the Cif:Nedd8 complex - Photorhabdus luminescens Cycle Inhibiting Factor in complex with human Nedd8== | | ==Structure of the Cif:Nedd8 complex - Photorhabdus luminescens Cycle Inhibiting Factor in complex with human Nedd8== |
| - | <StructureSection load='4fbj' size='340' side='right' caption='[[4fbj]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='4fbj' size='340' side='right'caption='[[4fbj]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fbj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Pholl Pholl]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FBJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FBJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fbj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Photorhabdus_laumondii_subsp._laumondii_TTO1 Photorhabdus laumondii subsp. laumondii TTO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FBJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f8c|4f8c]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=243265 PHOLL]), NEDD8 ([http://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=4fbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbj OCA], [https://pdbe.org/4fbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fbj RCSB], [https://www.ebi.ac.uk/pdbsum/4fbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbj 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=4fbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbj OCA], [http://pdbe.org/4fbj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fbj RCSB], [http://www.ebi.ac.uk/pdbsum/4fbj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NEDD8_HUMAN NEDD8_HUMAN]] Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.<ref>PMID:10318914</ref> <ref>PMID:10597293</ref> <ref>PMID:11953428</ref> | + | [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> |
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| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Pholl]] | + | [[Category: Large Structures]] |
| - | [[Category: Banfield, M J]] | + | [[Category: Photorhabdus laumondii subsp. laumondii TTO1]] |
| - | [[Category: Crow, A]] | + | [[Category: Banfield MJ]] |
| - | [[Category: Bacterial effector]] | + | [[Category: Crow A]] |
| - | [[Category: Cell cycle-protein binding complex]]
| + | |
| - | [[Category: Deamidation]]
| + | |
| - | [[Category: Effector-host target complex]]
| + | |
| - | [[Category: Glutamine deamidase]]
| + | |
| 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]
See Also
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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