A novel family of channel-forming, autotransporting, bacterial virulence factors.
Pathogenic bacteria produce virulence factors that cross the bacterial cell envelope from the cytoplasm to the extracellular milieu where they promote disease. The mechanisms of their export are poorly understood. We here characterize a family of autotransporter (AT) protein domains present at the C-termini of several nonhomologous Gram-negative bacterial virulence factors. The family consist of 18 sequenced protein domains, the functionally characterized members of which catalyze export of (1) proteases, (2) virulence-related cell adhesins, (3) mediators of actin-promoted bacterial motility, (4) cytotoxins and (5) tissue invasion proteins. We (1) establish that these AT domains are homologous, (2) multiply align their sequences, (3) derive an AT family-specific signature sequence, and (4) define the evolutionary relationships between members of the family. Secondary structural predictions as well as average hydropathy, average similarity and average amphipathicity plots have allowed us to propose a specific 14 beta-stranded barrel structural model that may be applicable to all protein members of the AT family. We suggest that the AT domains became associated with active virulence factor domains by interdomain fusion events that occurred during the evolution of these complex proteins.
Loveless
B J
BJ
Department of Biology, University of California at San Diego, La Jolla 92093-0116, USA.
Saier
M H
MH
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D016384:Consensus Sequence; D010450:Endopeptidases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D019143:Evolution, Molecular; D006090:Gram-Negative Bacteria / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014774:Virulence
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D010450:Endopeptidases