LAUSR

Significance Proteins attached to the surface of group A and group B streptococcal human pathogens that contain tandemly arrayed Rib domains have been associated with invasive infections and proposed as potential vaccine candidates. Here, we present structures of the Rib domain, both isolated and in tandem. The Rib domain structure is revealed as a rare example of “domain atrophy” from the much more common immunoglobulin-like fold. Tandem Rib domains adopt a head-to-tail arrangement with limited interdomain flexibility, suggesting that the previously observed, and proposed immune evasion-related, variation in Rib domain number is likely to result in differential projection of the N-terminal host colonization domain from the bacterial surface. Streptococcus groups A and B cause serious infections, including early onset sepsis and meningitis in newborns. Rib domain-containing surface proteins are found associated with invasive strains and elicit protective immunity in animal models. Yet, despite their apparent importance in infection, the structure of the Rib domain was previously unknown. Structures of single Rib domains of differing length reveal a rare case of domain atrophy through deletion of 2 core antiparallel strands, resulting in the loss of an entire sheet of the β-sandwich from an immunoglobulin-like fold. Previously, observed variation in the number of Rib domains within these bacterial cell wall-attached proteins has been suggested as a mechanism of immune evasion. Here, the structure of tandem domains, combined with molecular dynamics simulations and small angle X-ray scattering, suggests that variability in Rib domain number would result in differential projection of an N-terminal host-colonization domain from the bacterial surface. The identification of 2 further structures where the typical B-D-E immunoglobulin β-sheet is replaced with an α-helix further confirms the extensive structural malleability of the Rib domain.