title: The antigen 43 structure reveals a molecular Velcro-like mechanism of autotransporter-mediated bacterial clumping.
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.
authors: Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
authors: Begoña
authors: B
authors: Heras
authors: Makrina
authors: M
authors: Totsika
authors: Kate M
authors: KM
authors: Peters
authors: Jason J
authors: JJ
authors: Paxman
authors: Christine L
authors: CL
authors: Gee
authors: Russell J
authors: RJ
authors: Jarrott
authors: Matthew A
authors: MA
authors: Perugini
authors: Andrew E
authors: AE
authors: Whitten
authors: Mark A
authors: MA
authors: Schembri
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry*; D018830:Adhesins, Escherichia coli / Q000737:chemistry*; D000942:Antigens, Bacterial / Q000737:chemistry; D018441:Biofilms; D001692:Biological Transport; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014552:Urinary Tract Infections / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D000942:Antigens, Bacterial; C118376:antigen 43, E coli; C032774:antigen L
keywords: Ag43; structural biology; urinary tract infection; virulence factor