Publication Date:
2011-08-09
Description:
The intracellular pathogen Legionella pneumophila modulates the activity of host GTPases to direct the transport and assembly of the membrane-bound compartment in which it resides. In vitro studies have indicated that the Legionella protein DrrA post-translationally modifies the GTPase Rab1 by a process called AMPylation. Here we used mass spectrometry to investigate post-translational modifications to Rab1 that occur during infection of host cells by Legionella. Consistent with in vitro studies, DrrA-mediated AMPylation of a conserved tyrosine residue in the switch II region of Rab1 was detected during infection. In addition, a modification to an adjacent serine residue in Rab1 was discovered, which was independent of DrrA. The Legionella effector protein AnkX was required for this modification. Biochemical studies determined that AnkX directly mediates the covalent attachment of a phosphocholine moiety to Rab1. This phosphocholine transferase activity used CDP-choline as a substrate and required a conserved histidine residue located in the FIC domain of the AnkX protein. During infection, AnkX modified both Rab1 and Rab35, which explains how this protein modulates membrane transport through both the endocytic and exocytic pathways of the host cell. Thus, phosphocholination of Rab GTPases represents a mechanism by which bacterial FIC-domain-containing proteins can alter host-cell functions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206611/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206611/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mukherjee, Shaeri -- Liu, Xiaoyun -- Arasaki, Kohei -- McDonough, Justin -- Galan, Jorge E -- Roy, Craig R -- F32 AI082927/AI/NIAID NIH HHS/ -- R01 AI041699/AI/NIAID NIH HHS/ -- R01 AI041699-16/AI/NIAID NIH HHS/ -- R01 AI064559/AI/NIAID NIH HHS/ -- R01 AI064559-05/AI/NIAID NIH HHS/ -- R01-AI048770/AI/NIAID NIH HHS/ -- R01-AI064559/AI/NIAID NIH HHS/ -- U54-AI057158/AI/NIAID NIH HHS/ -- England -- Nature. 2011 Aug 7;477(7362):103-6. doi: 10.1038/nature10335.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, Yale University, New Haven, Connecticut, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21822290" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bacterial Proteins/*metabolism
;
COS Cells
;
Cercopithecus aethiops
;
Diacylglycerol Cholinephosphotransferase/*metabolism
;
Guanine Nucleotide Exchange Factors/metabolism
;
HEK293 Cells
;
Host-Pathogen Interactions/*physiology
;
Humans
;
Legionella pneumophila/*enzymology
;
Legionnaires' Disease/*enzymology/physiopathology
;
Mass Spectrometry
;
Protein Processing, Post-Translational
;
rab GTP-Binding Proteins/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
