6aoj
Crystal structure of Legionella pneumophila effector Ceg4 with N-terminal yeast Hog1p sequenceCrystal structure of Legionella pneumophila effector Ceg4 with N-terminal yeast Hog1p sequence
Structural highlights
FunctionPublication Abstract from PubMedHost colonization by Gram negative pathogens often involves delivery of bacterial proteins called effectors into the host cell. The pneumonia-causing pathogen Legionella pneumophila delivers more than 330 effectors into the host cell via its type IVB Dot/Icm secretion system. The collective functions of these proteins is the establishment of a replicative niche from which Legionella can recruit cellular materials to grow while evading lysosomal fusion inhibiting its growth. Using a combination of structural, biochemical, and in vivo approaches, we show that one of these translocated effector proteins, Ceg4, is a phosphotyrosine phosphatase harboring a haloacid dehalogenase hydrolase domain. Ceg4 could dephosphorylate a broad range of phosphotyrosine-containing peptides in vitro and attenuated activation of MAPK controlled pathways in both yeast and human cells. Our findings indicate that L. pneumophila's infectious program includes manipulation of phosphorylation cascades in key host pathways. The structural and functional features of the Ceg4 effector unraveled here, provide first insight into its function as a phosphotyrosine phosphatase, paving the way to further studies into L. pneumophila pathogenicity. The Legionella pneumophila effector Ceg4 is a phosphotyrosine phosphatase that attenuates activation of eukaryotic MAPK pathways.,Quaile AT, Stogios PJ, Egorova O, Evdokimova E, Valleau D, Nocek B, Kompella PS, Peisajovich S, Yakunin AF, Ensminger AW, Savchenko A J Biol Chem. 2018 Jan 4. pii: M117.812727. doi: 10.1074/jbc.M117.812727. PMID:29301934[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||