The antigen 43 structure reveals a molecular Velcrolike mechanism of autotransporter-mediated bacterial clumping

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-01, Vol.111 (1), p.457-462
• Main Authors: Heras, Begoña, Totsika, Makrina, Peters, Kate M., Paxman, Jason J., Gee, Christine L., Jarrottd, Russell J., Perugini, Matthew A., Whitten, Andrew E., Schembri, Mark A.
• Format: Article
• Language: English
• Subjects: Aggregation; Biofilms; Cell aggregates; Crystal structure; Dimers; Hydrogen bonds; Molecular interactions; Molecules; Passengers; Proteins
• ISSN: 0027-8424
• DOI: 10.1073/pnas.1311592111

Aggregation and biofilm formation are critical mechanisms for bacterial resistance to host immune factors and antibiotics. Autotransporter (AT) proteins, which represent the largest group of outer-membrane and secreted proteins in Gram-negative bacteria, contribute significantly to these phenotypes. Despite their abundance and role in bacterial pathogenesis, most AT proteins have not been structurally characterized, and there is a paucity of detailed information with regard to their mode of action. Here we report the structure—function relationships of Antigen 43 (Ag43a), a prototypic self-associating AT protein from uropathogenic Escherichia coli. The functional domain of Ag43a displays a twisted L-shaped β-helical structure firmly stabilized by a 3D hydrogenbonded scaffold. Notably, the distinctive Ag43a L shape facilitates self-association and cell aggregation. Combining all our data, we define a molecular "Velcro-like" mechanism of AT-mediated bacterial clumping, which can be tailored to fit different bacterial lifestyles such as the formation of biofilms.