Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection

Abstract

Streptococcusgroups 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.

Modelling structural rearrangements in proteins using Euclidean distance matrices

“…Domain atrophy is the abrupt loss of entire secondary structures in the core of a protein domain, resulting in a shorter version of the domain 3 . Although it is a rare evolutionary event, it has been described for some of the most widespread and conserved domain folds, like immunoglobulins (Ig) and TIM barrels 3,23 .…”

“…The domain atrophy in Rib domains involved the loss of a pair of beta strands core to its beta-sandwich topology 23 . The distance between the two ends of the deleted segment between positions 55 and 72 is, however, close enough so that a short linker can connect them, as captured by the EDM atrophy model shown in Figure 3D.…”

Periscope Proteins are variable length regulators of bacterial cell surface interactions

“…Having revealed the unusual repetitive, rod-like characteristics of both SasG (16) and Rib (17) in our previous studies, we used bioinformatic approaches to search for other cell-wall attached bacterial proteins with related organisation. A8AW49 (herein Sgo_0707) encoded by the gene Sgo_0707 from S. gordonii (Fig.…”

“…2B). The distributions of a, b, g inter-domain (17) angles ( fig. S5A) observed in the simulations of the Sgo_R3-4 construct (Fig.…”

“…Rib (17) form unusual highly elongated rods suggests that host-colonisation domains will be projected differing distances from the bacterial surface.…”