PROTEINS 2015* Surprising architectural variation of Autotransporter adhesins (#434)
Autotransporter (AT) proteins are the largest family of secreted and outer membrane proteins in Gram-negative bacteria. They are synthesised with an N-terminal signal sequence, an α-domain and a β-domain. The signal sequence directs passage across the inner membrane and the β-domain facilitates translocation of the α-domain to the cell surface. AT α-domains have important virulence-associated functions such as adhesion, biofilm formation, invasion, and toxicity. However, the mechanism by which most ATs promote virulence is poorly defined.
Most structurally determined AT α-domains are found to be built upon common right-handed β-helical scaffolds. Further work has shown that the addition of domains and loops that protrude from the β-solenoid provide ATs with their diverse functions. Our crystal structure of Antigen 43a from uropathogenic Escherichia coli (UPEC) was the first structure from an AIDA-I-type AT protein. AIDA-I-type proteins function as adhesins to promote bacterial aggregation, biofilm formation and/or cell adhesion. We demonstrated that modification of the β-helix scaffold itself was largely responsible for its functional mechanism. Specifically, its N-terminal dimerization domain and its unique L-shaped β-helix were critical for its ability to self-associate via a ‘Velcro-like’ mechanism that results in bacterial aggregation.
Here we present the structures of 2 new AIDA-I-type ATs; UpaB and TibA from UPEC and enterotoxigenic E. coli respectively. These structures show large differences and further plasticity in the β-helix scaffold. Our initial functional data supports that these alterations are critical to modulate their distinct virulence functions. Together this work reveals an unexpected structural diversity in the core β-helical scaffold of AIDA-I-type ATs which results in specific functions associated with pathogenesis.
