The C-terminal head domain of Burkholderia pseudomallei BpaC has a striking hydrophilic core with an extensive solvent network

Gram-negative pathogens like Burkholderia pseudomallei use trimeric autotransporter adhesins such as BpaC as key molecules in their pathogenicity. Our 1.4 angstrom crystal structure of the membrane-proximal part of the BpaC head domain shows that the domain is exclusively made of left-handed parallel beta-roll repeats. This, the largest such structure solved, has two unique features. First, the core, rather than being composed of the canonical hydrophobic Ile and Val, is made up primarily of the hydrophilic Thr and Asn, with two different solvent channels. Second, comparing BpaC to all other left-handed parallel beta-roll structures showed that the position of the head domain in the protein correlates with the number and type of charged residues. In BpaC, only negatively charged residues face the solvent-in stark contrast to the primarily positive surface charge of the left-handed parallel beta-roll type protein, YadA. We propose extending the definitions of these head domains to include the BpaC-like head domain as a separate subtype, based on its unusual sequence, position, and charge. We speculate that the function of left-handed parallel beta-roll structures may differ depending on their position in the structure.

Automated summary

Gram-negative pathogens like Burkholderia pseudomallei utilize trimeric autotransporter adhesins in their pathogenicity. We studied the structure of the membrane-proximal part of BpaC head domain and found unique features, such as composition of hydrophilic residues and the position in the protein. We suggest including this BpaC-like head domain as a separate subtype and speculate that the function may depend on its location in the structure.