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

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....

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Bibliographic Details
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, Jarrott, Russell J, Perugini, Matthew A, Whitten, Andrew E, Schembri, Mark A
Format: Article
Language:English
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1311592111