title: Trimeric autotransporters require trimerization of the passenger domain for stability and adhesive activity.
abstract: In recent years, structural studies have identified a number of bacterial, viral, and eukaryotic adhesive proteins that have a trimeric architecture. The prototype examples in bacteria are the Haemophilus influenzae Hia adhesin and the Yersinia enterocolitica YadA adhesin. Both Hia and YadA are members of the trimeric-autotransporter subfamily and are characterized by an internal passenger domain that harbors adhesive activity and a short C-terminal translocator domain that inserts into the outer membrane and facilitates delivery of the passenger domain to the bacterial surface. In this study, we examined the relationship between trimerization of the Hia and YadA passenger domains and the capacity for adhesive activity. We found that subunit-subunit interactions and stable trimerization are essential for native folding and stability and ultimately for full-level adhesive activity. These results raise the possibility that disruption of the trimeric architecture of trimeric autotransporters, and possibly other trimeric adhesins, may be an effective strategy to eliminate adhesive activity.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics and Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA.
authors.forename: Shane E
authors.initials: SE
authors.lastname: Cotter
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Surana
authors.forename: Susan
authors.initials: S
authors.lastname: Grass
authors.forename: Joseph W
authors.initials: JW
authors.lastname: St Geme
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001422:Bacterial Adhesion; D006193:Haemophilus influenzae / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D015008:Yersinia enterocolitica / Q000737:chemistry* / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; C429644:Hia adhesin; C064832:YadA protein, Yersinia