A steric antagonism of actin polymerization by a salmonella virulence protein.
Salmonella spp. require the ADP-ribosyltransferase activity of the SpvB protein for intracellular growth and systemic virulence. SpvB covalently modifies actin, causing cytoskeletal disruption and apoptosis. We report here the crystal structure of the catalytic domain of SpvB, and we show by mass spectrometric analysis that SpvB modifies actin at Arg177, inhibiting its ATPase activity. We also describe two crystal structures of SpvB-modified, polymerization-deficient actin. These structures reveal that ADP-ribosylation does not lead to dramatic conformational changes in actin, suggesting a model in which this large family of toxins inhibits actin polymerization primarily through steric disruption of intrafilament contacts.
Margarit
S Mariana
SM
Laboratory of Structural Microbiology, Rockefeller University, New York, New York 10021, USA.
Davidson
Walter
W
Frego
Lee
L
Stebbins
C Erec
CE
D036002:ADP Ribose Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012475:Salmonella / Q000737:chemistry*; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D000199:Actins; D037521:Virulence Factors; D036002:ADP Ribose Transferases; C415223:spvB protein, Salmonella enterica virulence plasmid