3gqm

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Cell Inhibiting Factor (Cif) from Burkholderia pseudomallei (CifBp)

Structural highlights

3gqm is a 2 chain structure with sequence from Burkholderia pseudomallei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CIF_BURPS 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:20688984, PubMed:19225106). 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) (PubMed:20688984, PubMed:21903097). 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 (PubMed:23175788). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (PubMed:20688984). Also regulates the host NF-kappa-B signaling via activation of MAPK/ERK cascade: activation of host MAPK/ERK cascade is independent of CRL complexes inhibition, suggesting that Cif has other host protein targets than NEDD8 (PubMed:28166272, PubMed:29848489).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Cui J, Yao Q, Li S, Ding X, Lu Q, Mao H, Liu L, Zheng N, Chen S, Shao F. Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family. Science. 2010 Sep 3;329(5996):1215-8. doi: 10.1126/science.1193844. Epub 2010 Aug, 5. PMID:20688984 doi:http://dx.doi.org/10.1126/science.1193844
↑ Boh BK, Ng MY, Leck YC, Shaw B, Long J, Sun GW, Gan YH, Searle MS, Layfield R, Hagen T. Inhibition of cullin RING ligases by cycle inhibiting factor: evidence for interference with Nedd8-induced conformational control. J Mol Biol. 2011 Oct 21;413(2):430-7. doi: 10.1016/j.jmb.2011.08.030. Epub 2011, Aug 29. PMID:21903097 doi:http://dx.doi.org/10.1016/j.jmb.2011.08.030
↑ Yao Q, Cui J, Wang J, Li T, Wan X, Luo T, Gong YN, Xu Y, Huang N, Shao F. Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20395-400. doi:, 10.1073/pnas.1210831109. Epub 2012 Nov 21. PMID:23175788 doi:http://dx.doi.org/10.1073/pnas.1210831109
↑ Ng MY, Wang M, Casey PJ, Gan YH, Hagen T. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif). PLoS One. 2017 Feb 6;12(2):e0171464. doi: 10.1371/journal.pone.0171464., eCollection 2017. PMID:28166272 doi:http://dx.doi.org/10.1371/journal.pone.0171464
↑ Ng MY, Gan YH, Hagen T. Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif). Biol Open. 2018 Jul 16;7(7). pii: bio.028225. doi: 10.1242/bio.028225. PMID:29848489 doi:http://dx.doi.org/10.1242/bio.028225
↑ Crow A, Race PR, Jubelin G, Varela Chavez C, Escoubas JM, Oswald E, Banfield MJ. Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei. PLoS ONE. 2009;4(5):e5582. Epub 2009 May 18. PMID:19440549 doi:10.1371/journal.pone.0005582

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3gqm"

Categories: Burkholderia pseudomallei | Large Structures | Banfield MJ | Crow A

@@ Line 1: / Line 1: @@
 ==Crystal structure of Cell Inhibiting Factor (Cif) from Burkholderia pseudomallei (CifBp)==
-<StructureSection load='3gqm' size='340' side='right' caption='[[3gqm]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='3gqm' size='340' side='right'caption='[[3gqm]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3gqm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GQM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GQM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3gqm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GQM FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gqj|3gqj]], [[3eit|3eit]]</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]] 2.1&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BPSS1385 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28450 Burkholderia pseudomallei])</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=3gqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gqm OCA], [https://pdbe.org/3gqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gqm RCSB], [https://www.ebi.ac.uk/pdbsum/3gqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gqm 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=3gqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gqm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gqm RCSB], [http://www.ebi.ac.uk/pdbsum/3gqm PDBsum]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/CIF_BURPS CIF_BURPS] 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:20688984, PubMed:19225106). 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) (PubMed:20688984, PubMed:21903097). 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 (PubMed:23175788). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (PubMed:20688984). Also regulates the host NF-kappa-B signaling via activation of MAPK/ERK cascade: activation of host MAPK/ERK cascade is independent of CRL complexes inhibition, suggesting that Cif has other host protein targets than NEDD8 (PubMed:28166272, PubMed:29848489).<ref>PMID:19225106</ref> <ref>PMID:19308257</ref> <ref>PMID:20688984</ref> <ref>PMID:21903097</ref> <ref>PMID:23175788</ref> <ref>PMID:28166272</ref> <ref>PMID:29848489</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3gqm" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 20: / Line 23: @@
 </StructureSection>
 [[Category: Burkholderia pseudomallei]]
-[[Category: Banfield, M J]]
+[[Category: Large Structures]]
-[[Category: Crow, A]]
+[[Category: Banfield MJ]]
-[[Category: Cell inhibiting factor]]
+[[Category: Crow A]]
-[[Category: Cif]]
-[[Category: Cifbp]]
-[[Category: Unknown function]]

3gqm

From Proteopedia

Current revision

Crystal structure of Cell Inhibiting Factor (Cif) from Burkholderia pseudomallei (CifBp)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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