Structural biology of gram‐positive bacterial adhesins

Abstract

The structural biology of Gram-positive cell surface adhesins is an emerging field of research, whereas Gram-negative pilus assembly and anchoring have been extensively investigated and are well understood. Gram-positive surface proteins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and individual proteins that assemble into long, hair-like organelles known as pili have similar features at the primary sequence level as well as at the tertiary structural level. Some of these conserved features are essential for their transportation from the cytoplasm and for cell wall anchoring. More importantly, the MSCRAMMs and the individual pilins are assembled with building blocks that are variants of structural modules used for human immunoglobulins. MSCRAMMs target the host's extracellular matrix proteins, such as collagen, fibrinogen, and fibronectin, and they have received considerable attention from structural biologists in the last decade, who have primarily been interested in understanding their interactions with host tissue. The recent focus is on the newly discovered pili of Gram-positive bacteria, and in this review, we highlight the advances in understanding of the individual pilus constituents and their associations and stress the similarities between the individual pilins and surface proteins.

The Choline-binding Protein PspC of Streptococcus pneumoniae Interacts with the C-terminal Heparin-binding Domain of Vitronectin

“…the "tandem ␤-zipper," the "dock, lock, and latch," and the "collagen hug" models. The two latter are characterized by two subdomains cooperating to capture the ligand molecule and a third subdomain securing the binding (44). These models, however, rely on the presence of Ig-like folds formed by antiparallel ␤-strands and hydrophobic interactions between adhesin and ligand.…”

Structural Basis of Pilus Anchoring by the Ancillary Pilin RrgC of Streptococcus pneumoniae

“…Minor pilins such as RrgC, however, do not display such sequences. These molecules, and most notably the base pilin, use an exposed Lys side chain to link to other pilus-related molecules (16,49). This is the case for minor pilins SpaB from C. diphtheriae, FctB from a group A Streptococcus strain, and GBS52 from S. agalactiae, which become covalently incorporated into the pilus through exposed Lys residues located in flexible loop regions (28, 49 -51).…”

“…Despite the fact that the nucleophilic Lys residue is yet to be identified in RrgC, the comparison of its structure with that of GBS52 points clearly to a candidate residue. In GBS52, Lys-148, located in the flexible linker region between D1 and D2, lies within a pilin-like motif (IYPK) and has been suggested as being responsible for linking GBS52 to partner molecules (49). Likewise, Lys-142 of RrgC is located at precisely the same position and points into solvent, much like its GBS52 counterpart.…”

Autocatalytically generated Thr-Gln ester bond cross-links stabilize the repetitive Ig-domain shaft of a bacterial cell surface adhesin

“…1A). The 11 repeat domains are predicted to each have an all β-strand IgG-like fold such as is commonly found in both Gram-positive pili and other MSCRAMMs (6,16). The stalk domain sequences are highly conserved with a minimum pairwise sequence identity of 85%.…”