Protein Secretion in Gram-Negative Bacteria via the Autotransporter Pathway^*

Autotransporters are a large and diverse superfamily of proteins produced by pathogenic gram-negative bacteria that are composed of an N-terminal passenger domain, which typically harbors a virulence function, and a C-terminal β domain. It has long been known that the β domain anchors the protein to the outer membrane and facilitates transport of the passenger domain into the extracellular space. Despite the apparent simplicity of the autotransporter pathway, several aspects of autotransporter biogenesis remain poorly understood, most notably the mechanism by which the passenger domain is translocated across the outer membrane. Here we review recent evidence that the enormous sequence diversity of both passenger and β domains belies a remarkable conservation of structure. We also discuss insights into each stage of autotransporter biogenesis that have emerged from recent structural, biochemical, and imaging studies.