biostudies-literatureWang ZNIAID NIH HHS53https://www.ebi.ac.uk/biostudies/studies/S-EPMC6175885biostudies-literatureUnknown4Posttranslational modification of key host proteins by virulence factors is an important theme in bacterial pathogenesis. A remarkable example is the reversible modifications of the small GTPase Rab1 by multiple effectors of the bacterial pathogen <i>Legionella pneumophila</i>. Previous studies have shown that the effector SetA, dependent on a functional glucosyltransferase domain, interferes with host secretory pathways. However, the enzymatic substrate(s) of SetA in host cells remains unknown. Here, by using cross-linking mass spectrometry we uncovered Rab1 as the target of SetA during <i>L. pneumophila</i> infection. Biochemical studies establish that SetA covalently attaches a glucose moiety to Thr₇₅ within the switch II region of Rab1, inhibiting its intrinsic GTPase activiCell discoveryRegulation of the small GTPase Rab1 function by a bacterial glucosyltransferase.PMC6175885R01 AI127465McCloskey ACheng SLiu XLiu YWu MXue CLuo ZQFu JYu ZWang ZfalseRegulation of the small GTPase Rab1 function by a bacterial glucosyltransferase.Posttranslational modification of key host proteins by virulence factors is an important theme in bacterial pathogenesis. A remarkable example is the reversible modifications of the small GTPase Rab1 by multiple effectors of the bacterial pathogen <i>Legionella pneumophila</i>. Previous studies have shown that the effector SetA, dependent on a functional glucosyltransferase domain, interferes with host secretory pathways. However, the enzymatic substrate(s) of SetA in host cells remains unknown. Here, by using cross-linking mass spectrometry we uncovered Rab1 as the target of SetA during <i>L. pneumophila</i> infection. Biochemical studies establish that SetA covalently attaches a glucose moiety to Thr₇₅ within the switch II region of Rab1, inhibiting its intrinsic GTPase activi2018-01-01T00:00:00Z20182025-04-21T21:52:42.799Z2019-03-27T00:02:41ZS-EPMC61758853032394810.1038/s41421-018-0055-9