title: Yersinia effector YopO uses actin as bait to phosphorylate proteins that regulate actin polymerization.
abstract: 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.
authors: 1] Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore. [2] Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors: Wei Lin
authors: 0000000310487556
authors: WL
authors: Lee
authors: 1] Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Diamond Light Source, Oxfordshire, UK.
authors: Jonathan M
authors: JM
authors: Grimes
authors: 1] Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore. [2] Department of Biochemistry, National University of Singapore, Singapore.
authors: Robert C
authors: RC
authors: Robinson
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010587:Phagocytosis; D010766:Phosphorylation; D058105:Polymerization; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015008:Yersinia enterocolitica / Q000378:metabolism
chemical_list: D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C415206:YopO protein, Yersinia enterocolitica; D017346:Protein Serine-Threonine Kinases