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SpyA is a membrane‐bound ADP‐ribosyltransferase of Streptococcus pyogenes which modifies a streptococcal peptide, SpyB
Author(s) -
Korotkova Natalia,
Hoff Jessica S.,
Becker Devon M.,
Quinn John Kyle Heggen,
Icenogle Laura M.,
Moseley Steve L.
Publication year - 2012
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2012.07979.x
Subject(s) - biology , streptococcus pyogenes , transmembrane protein , peptide sequence , membrane protein , signal peptide , peptide , virulence , translation (biology) , homology (biology) , amino acid , gene , biochemistry , messenger rna , membrane , receptor , genetics , bacteria , staphylococcus aureus
Summary All sequenced genomes of Streptococcus pyogenes (Group A Streptococcus , GAS) encode a protein, SpyA, with homology to C3‐like ADP‐ribosyltransferase toxins. SpyA is a novel virulence factor which plays a role in pathogenesis in a mouse model of soft‐tissue infection. In this study we demonstrate that SpyA is a surface‐exposed membrane protein which is anchored to the streptococcal membrane by an N‐terminal transmembrane sequence. We identified a small gene upstream of spyA , designated spyB , which encodes a peptide of 35 amino acids, and is co‐transcribed with spyA . Expression of spyBA is strongly influenced by translational coupling: mutational inactivation of spyB translation completely abolishes translation of spyA . spyB expression increases with increasing cell density and reaches its maximum at late exponential growth phase. The SpyB N‐terminus is predicted to fold into an amphipathic α‐helix, a structural motif that targets a protein to the cytoplasmic membrane. Consistent with the prediction, we found that a SpyB fusion with peptide affinity tags is located in the streptococcal membrane. An ADP‐ribosylation assay with recombinant SpyA demonstrated that SpyA modifies SpyB. Thus, our study suggests that ADP‐ribosylation of SpyB may be an important function of SpyA.