The turn of the screw: Variations of the abundant β-solenoid motif in passenger domains of Type V secretory proteins

Abstract

Many virulence factors of gram-negative bacteria are secreted by the Type V secretion system via the autotransporter (AT) and two-partner secretion (TPS) pathways. AT proteins effect their own secretion. They comprise three domains: the amino-terminal leader sequence; the secreted passenger domain; and the translocator domain that forms the secretory channel. In the TPS pathway, the passenger and translocator domains are translated as separate proteins. In a previous publication, we proposed a β-helical structure for the TPS passenger domain of the filamentous hemagglutinin (FHA) of Bordetella pertussis which contains two tracts, R1 and R2, of 19-residue sequence repeats and built molecular models for the R1 and R2 β-helices. Here, we compare the structure predicted for R1 with the recently determined crystal structure of a fragment containing three R1 repeats and find close agreement, with an RMSD of 1.1 Å. In the interim, the number of known AT and TPS protein sequences has increased to >1000. To investigate the incidence of β-helical structures among them, we carried out a sequence-based analysis and conclude that, despite wide diversity in the sizes and sequences of passenger domains, most of them contain β-solenoids that we classify into thirteen types based on distinctive properties of their β-coils (repeat length, numbers and lengths of β-strands and turns, cross-sectional shape, presence of specific residues in certain positions) summarized in a 2D coil template. Some coil types are typical for conventional AT proteins, others, for TPS or trimeric AT proteins. Some β-solenoids consist of stacked subdomains with coils of different types. To illustrate model-building from a coil template, we modeled a type-T4 β-solenoid for TibA of Escherichia coli which is predicted to have two conserved polar residues, Thr and Gln, in interior positions.