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

Heras, Begona, Totsika, Makrina, Peters, Kate M., Paxman, Jason J., Gee, Christine L., Jarrott, Russell J., Perugini, Matthew A., Whitten, Andrew E. and Schembri, Mark A. (2014) The antigen 43 structure reveals a molecular Velcrolike mechanism of autotransporter-mediated bacterial clumping. Proceedings of the National Academy of Sciences of the United States of America, 111 1: 457-462. doi:10.1073/pnas.1311592111


Author Heras, Begona
Totsika, Makrina
Peters, Kate M.
Paxman, Jason J.
Gee, Christine L.
Jarrott, Russell J.
Perugini, Matthew A.
Whitten, Andrew E.
Schembri, Mark A.
Title The antigen 43 structure reveals a molecular Velcrolike mechanism of autotransporter-mediated bacterial clumping
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1073/pnas.1311592111
Open Access Status DOI
Volume 111
Issue 1
Start page 457
End page 462
Total pages 6
Place of publication Washington, DC United States
Publisher National Academy of Sciences
Language eng
Subject 1000 General
Abstract 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 beta-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.
Formatted abstract
 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.
Keyword Ag43
Structural biology
Urinary tract infection
Virulence factor
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1042651
DP1097032
DE120101143
9569864
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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