TY - JOUR
T1 - Yersinia effector YopO uses actin as bait to phosphorylate proteins that regulate actin polymerization
AU - Lee, Wei Lin
AU - Grimes, Jonathan M.
AU - Robinson, Robert C.
N1 - Funding Information:
We thank L. Burtnick and W. Burkholder for discussions and critical reading of the manuscript. W.L.L. and R.C.R. thank the A*STAR for support. We acknowledge the Joint Centre for Structural Biology, Singapore, which is supported by Nanyang Technological University and the Biomedical Research Council (BMRC) of A*STAR, for providing research facilities and P. Kaldis for providing help and facilities for the kinase assays. We thank the Diamond Light Source (proposal MX8423) for crystal screening and beamline BL13B1 at the National Synchrotron Radiation Research Center, Taiwan (NSRRC) for final data collection. The Wellcome Trust Centre for Human Genetics is supported by the Wellcome Trust Core award (090532/Z/09/Z). We thank L. Blanchoin (Institut de Recherches en Technologies et Sciences pour le Vivant) and M. Hernandez-Valladares (University of Liverpool) for reagents.
PY - 2015/3/6
Y1 - 2015/3/6
N2 - Pathogenic Yersinia species evade host immune systems through the injection of Yersinia outer proteins (Yops) into phagocytic cells. One Yop, YopO, also known as YpkA, induces actin-filament disruption, impairing phagocytosis. Here we describe the X-ray structure of Yersinia enterocolitica YopO in complex with actin, which reveals that YopO binds to an actin monomer in a manner that blocks polymerization yet allows the bound actin to interact with host actin-regulating proteins. SILAC-MS and biochemical analyses confirm that actin-polymerization regulators such as VASP, EVL, WASP, gelsolin and the formin diaphanous 1 are directly sequestered and phosphorylated by YopO through formation of ternary complexes with actin. This leads to a model in which YopO at the membrane sequesters actin from polymerization while using the bound actin as bait to recruit, phosphorylate and misregulate host actin-regulating proteins to disrupt phagocytosis.
AB - Pathogenic Yersinia species evade host immune systems through the injection of Yersinia outer proteins (Yops) into phagocytic cells. One Yop, YopO, also known as YpkA, induces actin-filament disruption, impairing phagocytosis. Here we describe the X-ray structure of Yersinia enterocolitica YopO in complex with actin, which reveals that YopO binds to an actin monomer in a manner that blocks polymerization yet allows the bound actin to interact with host actin-regulating proteins. SILAC-MS and biochemical analyses confirm that actin-polymerization regulators such as VASP, EVL, WASP, gelsolin and the formin diaphanous 1 are directly sequestered and phosphorylated by YopO through formation of ternary complexes with actin. This leads to a model in which YopO at the membrane sequesters actin from polymerization while using the bound actin as bait to recruit, phosphorylate and misregulate host actin-regulating proteins to disrupt phagocytosis.
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U2 - 10.1038/nsmb.2964
DO - 10.1038/nsmb.2964
M3 - Article
C2 - 25664724
AN - SCOPUS:84924101878
VL - 22
SP - 248
EP - 255
JO - Nature Structural Biology
JF - Nature Structural Biology
SN - 1545-9993
IS - 3
ER -