antigen 43 structure reveals a molecular Velcro-like mechanism of autotransporter-mediated bacterial clumping

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 1; pp. 457 - 462
• Main Authors: Heras, Begoña, Totsika, Makrina, Peters, Kate M, Paxman, Jason J, Gee, Christine L, Jarrott, Russell J, Perugini, Matthew A, Whitten, Andrew E, Schembri, Mark A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 07.01.2014; National Acad Sciences
• Subjects: Adhesins, Bacterial - chemistry; Adhesins, Escherichia coli - chemistry; Antibiotics; Antigens, Bacterial - chemistry; Biofilms; Biological Sciences; Biological Transport; Cloning, Molecular; Crystallography, X-Ray; E coli; Escherichia coli; Genotype & phenotype; Gram-negative bacteria; Hydrogen Bonding; Hydrogen bonds; Mutation; Pathogenesis; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Urinary Tract Infections - microbiology; Uropathogenic Escherichia coli - metabolism; X-Ray Diffraction; Ag43; structural biology; virulence factor; urinary tract infection
• ISSN: 0027-8424; 1091-6490
• 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 hydrogen-bonded 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.