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Journal of Bacteriology, August 2006, p. 5400-5407, Vol. 188, No. 15
0021-9193/06/$08.00+0     doi:10.1128/JB.00164-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Trimeric Autotransporters Require Trimerization of the Passenger Domain for Stability and Adhesive Activity

Shane E. Cotter,1 Neeraj K. Surana,1 Susan Grass,2 and Joseph W. St. Geme III2*

Edward Mallinckrodt Department of Pediatrics and Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110,1 Departments of Pediatrics and Molecular Genetics and Microbiology, Duke University Medical Center, Children's Health Center, Durham, North Carolina 277102

Received 30 January 2006/ Accepted 12 May 2006

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.


* Corresponding author. Mailing address: Department of Pediatrics, Duke University Medical Center, Children's Health Center, Room T901, DUMC 3352, Durham, NC 27710. Phone: (919) 681-4080. Fax: (919) 681-2714. E-mail: j.stgeme{at}duke.edu.


Journal of Bacteriology, August 2006, p. 5400-5407, Vol. 188, No. 15
0021-9193/06/$08.00+0     doi:10.1128/JB.00164-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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