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4bet

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Revision as of 22:09, 24 December 2014

Crystal structure of the Legionella pneumophila FIC domain-containing effector AnkX protein (inactive H229A mutant) in complex with cytidine-diphosphate-choline

Structural highlights

4bet is a 2 chain structure with sequence from Legionella pneumophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4bep, 4ber, 4bes
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[ANKX_LEGPH] Virulence effector that plays a role in hijacking the host vesicular trafficking by recruiting the small guanosine triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella-containing vacuole (LCVs). Acts as a phosphocholine transferase by mediating the addition of phosphocholine to Ser residues of host RAB1 (RAB1A, RAB1B or RAB1C) and RAB35, leading to displacement of GDP dissociation inhibitors (GDI). Phosphocholination of target proteins also impairs accessibility to GTPase effector LepB. Can act on both GDP-bound and GTP-bound Rab proteins.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The FIC motif and the eukaryotic-like ankyrin repeats are found in many bacterial type IV effectors, yet little is known about how these domains enable bacteria to modulate host cell functions. Bacterial FIC domains typically bind ATP and transfer adenosine monophosphate moiety onto target proteins. The ankyrin repeat-containing protein AnkX encoded by the intracellular pathogen Legionella pneumophila is unique in that its FIC domain binds to CDP-choline and transfers a phosphocholine residue onto proteins in the Rab1 GTPase family. By determining the structures of unbound AnkX and AnkX with bound CDP-choline, CMP/phosphocholine and CMP, we demonstrate that the orientation of substrate binding in relation to the catalytic FIC motif enables this protein to function as a phosphocholinating enzyme rather than a nucleotidyl transferase. Additionally, the structure reveals that the ankyrin repeats mediate scaffolding interactions that resemble those found in protein-protein interactions, but are unprecedented in intramolecular interactions. Together with phosphocholination experiments, our structures unify a general phosphoryl transferase mechanism common to all FIC enzymes that should be conserved from bacteria to human.

Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain.,Campanacci V, Mukherjee S, Roy CR, Cherfils J EMBO J. 2013 Apr 9. doi: 10.1038/emboj.2013.82. PMID:23572077^[6]

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

References

↑ Pan X, Luhrmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science. 2008 Jun 20;320(5883):1651-4. doi: 10.1126/science.1158160. PMID:18566289 doi:10.1126/science.1158160
↑ Tan Y, Arnold RJ, Luo ZQ. Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21212-7. doi:, 10.1073/pnas.1114023109. Epub 2011 Dec 7. PMID:22158903 doi:10.1073/pnas.1114023109
↑ Mukherjee S, Liu X, Arasaki K, McDonough J, Galan JE, Roy CR. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature. 2011 Aug 7;477(7362):103-6. doi: 10.1038/nature10335. PMID:21822290 doi:10.1038/nature10335
↑ Goody PR, Heller K, Oesterlin LK, Muller MP, Itzen A, Goody RS. Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins. EMBO J. 2012 Feb 3;31(7):1774-84. doi: 10.1038/emboj.2012.16. PMID:22307087 doi:10.1038/emboj.2012.16
↑ Oesterlin LK, Goody RS, Itzen A. Posttranslational modifications of Rab proteins cause effective displacement of GDP dissociation inhibitor. Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5621-6. doi:, 10.1073/pnas.1121161109. Epub 2012 Mar 12. PMID:22411835 doi:10.1073/pnas.1121161109
↑ Campanacci V, Mukherjee S, Roy CR, Cherfils J. Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain. EMBO J. 2013 Apr 9. doi: 10.1038/emboj.2013.82. PMID:23572077 doi:10.1038/emboj.2013.82

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/4bet"

@@ Line 7: / Line 7: @@
 <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=4bet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bet OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bet RCSB], [http://www.ebi.ac.uk/pdbsum/4bet PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/ANKX_LEGPH ANKX_LEGPH]] Virulence effector that plays a role in hijacking the host vesicular trafficking by recruiting the small guanosine triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella-containing vacuole (LCVs). Acts as a phosphocholine transferase by mediating the addition of phosphocholine to Ser residues of host RAB1 (RAB1A, RAB1B or RAB1C) and RAB35, leading to displacement of GDP dissociation inhibitors (GDI). Phosphocholination of target proteins also impairs accessibility to GTPase effector LepB. Can act on both GDP-bound and GTP-bound Rab proteins.<ref>PMID:18566289</ref> <ref>PMID:22158903</ref> <ref>PMID:21822290</ref> <ref>PMID:22307087</ref> <ref>PMID:22411835</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4bet

From Proteopedia

Revision as of 22:09, 24 December 2014

Crystal structure of the Legionella pneumophila FIC domain-containing effector AnkX protein (inactive H229A mutant) in complex with cytidine-diphosphate-choline

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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