title: ACTIN-DIRECTED TOXIN. ACD toxin-produced actin oligomers poison formin-controlled actin polymerization.
abstract: The actin cross-linking domain (ACD) is an actin-specific toxin produced by several pathogens, including life-threatening spp. of Vibrio cholerae, Vibrio vulnificus, and Aeromonas hydrophila. Actin cross-linking by ACD is thought to lead to slow cytoskeleton failure owing to a gradual sequestration of actin in the form of nonfunctional oligomers. Here, we found that ACD converted cytoplasmic actin into highly toxic oligomers that potently "poisoned" the ability of major actin assembly proteins, formins, to sustain actin polymerization. Thus, ACD can target the most abundant cellular protein by using actin oligomers as secondary toxins to efficiently subvert cellular functions of actin while functioning at very low doses.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Heisler
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Kudryashova
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Grinevich
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Suarez
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Winkelman
authors.affiliation: Section of Pulmonary and Critical Care and Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Birukov
authors.affiliation: Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Sainath R
authors.initials: SR
authors.lastname: Kotha
authors.affiliation: Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Narasimham L
authors.initials: NL
authors.lastname: Parinandi
authors.affiliation: Department of Physics, Lehigh University, Bethlehem, PA 18015, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vavylonis
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Kovar
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu.
authors.forename: Dmitri S
authors.initials: DS
authors.lastname: Kudryashov
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity*; D002460:Cell Line; D005326:Fetal Proteins / Q000037:antagonists & inhibitors*; D000080865:Formins; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D058105:Polymerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D000199:Actins; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C030325:anthrax toxin