Identification of a domain in Bordetella pertussis adenylyl cyclase important for subunit interactions and cell invasion activity.
Bordetella pertussis produces a calmodulin-stimulated adenylyl cyclase that invades animal cells and raises intracellular cAMP levels. The enzyme does not enter animal cells by receptor-mediated endocytosis, but the mechanism for invasion of animal cells has not been defined. We have proposed that the 177 kDa adenylyl cyclase is proteolyzed to a 45 kDa catalytic subunit and one or more polypeptides (invasive factor) that facilitate entry of the catalytic subunit into animal cells. In this study, we report the identification of a sequence of amino acids within the adenylyl cyclase catalytic subunit that is important for entry of the enzyme into eukaryotic cells. A synthetic peptide corresponding to amino acids 313-339 within the catalytic subunit was shown to inhibit invasion of neuroblastoma cells by the adenylyl cyclase. In addition, this peptide inhibited the association of the catalytic subunit with invasive factor. We propose that this domain is a site for interaction between the catalytic subunit and invasive factor.
Oldenburg
D J
DJ
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Storm
D R
DR
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000502:physiology; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D001886:Bordetella pertussis / Q000201:enzymology* / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis; D006460:Hemolysin Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D010455:Peptides / Q000737:chemistry; D011498:Protein Precursors / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured
D037361:Adenylate Cyclase Toxin; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D010455:Peptides; D011498:Protein Precursors; D000242:Cyclic AMP; D000262:Adenylyl Cyclases