Structure of the Head of the Bartonella Adhesin BadA

Abstract

Trimeric autotransporter adhesins (TAAs) are a major class of proteins by which pathogenic proteobacteria adhere to their hosts. Prominent examples include Yersinia YadA, Haemophilus Hia and Hsf, Moraxella UspA1 and A2, and Neisseria NadA. TAAs also occur in symbiotic and environmental species and presumably represent a general solution to the problem of adhesion in proteobacteria. The general structure of TAAs follows a head-stalk-anchor architecture, where the heads are the primary mediators of attachment and autoagglutination. In the major adhesin of Bartonella henselae, BadA, the head consists of three domains, the N-terminal of which shows strong sequence similarity to the head of Yersinia YadA. The two other domains were not recognizably similar to any protein of known structure. We therefore determined their crystal structure to a resolution of 1.1 Å. Both domains are β-prisms, the N-terminal one formed by interleaved, five-stranded β-meanders parallel to the trimer axis and the C-terminal one by five-stranded β-meanders orthogonal to the axis. Despite the absence of statistically significant sequence similarity, the two domains are structurally similar to domains from Haemophilus Hia, albeit in permuted order. Thus, the BadA head appears to be a chimera of domains seen in two other TAAs, YadA and Hia, highlighting the combinatorial evolutionary strategy taken by pathogens.

Complete fiber structures of complex trimeric autotransporter adhesins conserved in enterobacteria

“…In architecturally complex adhesins, head and stalk segments may alternate several times before the anchor is reached (12). Whereas head and stalk are assembled from an array of analogous domains (13), the anchor is homologous in all TAAs and represents the defining element of this protein family (2). It trimerizes in the outer membrane to form a 12-stranded β-barrel pore (14), through which the head and the stalk exit the periplasm, thus giving rise to the name "autotransporter."…”

“…Several head structures, from YadA (15), Hia (16), BadA (13), and BpaA (17), revealed different trimeric complexes with novel folds. Partial stalk structures from UspA1 (18), SadA (19), and YadA (20) substantiated earlier predictions that coiled coils are the dominant structural motif of TAA stalks, albeit sometimes with noncanonical properties such as unusual periodicities or ion binding sites in their core.…”

“…Despite their strong sequence divergence, structures of homologous TAA domains are so closely conserved that one structure can be used to solve the next one by molecular replacement (13,21); this characteristic, and the fact that the domains can be predicted from sequence using state-of-the-art homology detection methods (12), prompted us to suggest a dictionary approach to understand the structure of TAAs, given that their flexibility and extreme length otherwise precludes their analysis by high-resolution methods. We proposed to solve representatives for all TAA domains defined from sequence analysis, which could then be used to model full TAA fibers from fragments (13,22).…”

“…We proposed to solve representatives for all TAA domains defined from sequence analysis, which could then be used to model full TAA fibers from fragments (13,22). Strictly speaking, the term "domain," which has been developed on globular proteins to denote independently folding units, does not fully describe the structural elements of TAA or oligomeric fibers in general.…”

Correlation of in situ mechanosensitive responses of the Moraxella catarrhalis adhesin UspA1 with fibronectin and receptor CEACAM1 binding

“…These monomers form elongated, trimeric structures extending up to 800 Å from the cell surface, where they form a distinctive and densely packed molecular coating (3). Sequence homology studies (3,4) indicate that UspA1 belongs to a family of bacterial adhesins termed either oligomeric coiled-coil adhesins (Oca) or trimeric autotransporter adhesins (TAAs). These adhesins are believed to share a modular structure consisting of a variable β-propeller amino terminal head group, extended coiled-coil stalk region, and a membrane β-barrel anchor domain at the carboxy terminus (reviewed in ref.…”