4fbj

Structure of the Cif:Nedd8 complex - Photorhabdus luminescens Cycle Inhibiting Factor in complex with human Nedd8Structure of the Cif:Nedd8 complex - Photorhabdus luminescens Cycle Inhibiting Factor in complex with human Nedd8

Structural highlights

4fbj is a 2 chain structure with sequence from Homo sapiens and Photorhabdus laumondii subsp. laumondii TTO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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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OCA

[1] 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

[2] 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

[3] 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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