Hydrophobic Patch is Indispensable for Passenger Domain Translocation of Autotransporter

Abstract

Whooping cough (pertussis) is a highly contagious, acute respiratory illness of humans caused by the gram-negative bacterial pathogen Bordetella pertussis. Autotransporter (AT) BrkA is an important B. pertussis virulence factor that confers serum resistance and mediates adherence. Here we present the crystal structure of B. pertussis BrkA β domain at 3A resolution. It shows that a hairpin-like structural motif from an adjacent molecule is inserted into the central pore of the β barrel. An undiscovered hydrophobic cavity formed by the hydrophobic patches on the loop L4, β-strands S5 and S6 adopts a ubiquitous structural characteristic of all AT β domains. A mutagenesis study proved that the hydrophobic cavity is indispensable for BrkA passenger domain translocation. This structure helps in understanding the molecular mechanism of AT secretion and provides a potential target for anti-pertussis drug design.