Structure and Biology of Trimeric Autotransporter Adhesins

Abstract

Trimeric autotransporter adhesins (TAAs) are a family of secreted Gram-negative bacterial outer membrane (OM) proteins. These obligate homotrimeric proteins share a common molecular organisation, consisting of a N-terminal "passenger" domain followed by a C-terminal translocation unit/membrane anchor. All described TAAs act as adhesins. The passenger domain is responsible for specific adhesive and other activities of the protein and has a modular architecture. Its globular head domain(s), where ligands often bind, are projected away from the bacterial surface by an extended triple α-helical coiled coil stalk attached to the β-barrel anchor. The head domains appear to be constructed from a limited set of subdomains. The β-barrel anchor is the only part of the protein strictly conserved between family members. It appears that the extracellular export of the passenger does not require an external energy source or auxiliary proteins, though recent data indicate that an OM complex (the Bam complex) is involved in passenger domain secretion. The ability to bind to a variety of host molecules such as collagen, fibronectin, laminin or cell surface receptors via a structurally diverse elements suggests that TAAs have evolved a unique mechanism which closely links structure to folding and function.

In silico prediction of

“…EmaA is widespread among A. actinomycetemcomitans strains [56] and belongs to the family of trimeric autotransporter adhesins (TAAs) [57]. TAAs are a group of homotrimeric virulence-related proteins in Gram-negative bacteria that primarily act as adhesins [58]. Interestingly, the Neisseria adhesin A (NadA) protein from MenB, which is one of the proteins in the recently approved 4CMenB vaccine (Bexsero®), also belongs to this family of TAAs [59], further suggesting a protective potential of Gab_2312.…”

The Haemophilus Cryptic Genospecies Cha Adhesin Has at Least Two Variants That Differ in Host Cell Binding, Bacterial Aggregation, and Biofilm Formation Properties

“…Cha is a member of the trimeric autotransporter adhesin (TAA) family, a group of surface-localized proteins that are characterized by an N-terminal signal sequence, an internal passenger domain, a C-terminal ␤-barrel outer membrane anchor domain, and a trimeric architecture (11). TAA proteins transit the inner membrane via the Sec secretion system and undergo cleavage of the N-terminal signal peptide.…”

“…While the ␤-barrel domain is the only conserved portion among the TAA family, all members described to date have adhesive activity and share a repetitive structural domain organization, typically a coiled-coil stalk and a spherical adhesive tip (16). The prototypic TAA adhesive domain is the YadA-like head (Ylh) domain, which forms left-handed ␤-roll structures and is found in several TAA proteins in different bacterial species (11,17). A single cluster of repetitive Ylh amino acid motifs forms the globular Ylh domain head of the Yersinia enterocolitica YadA adhesin (18) and appears to be responsible for YadAmediated adherence to collagen, as mutation of conserved amino acids in the Ylh domain eliminates adherence (18,19).…”

Characterization and Functional Analysis of AatB, a Novel Autotransporter Adhesin and Virulence Factor of Avian Pathogenic Escherichia coli

“…In principal, all members of the AT family share conserved structural features: a secretion signal peptide in the N terminus, a conserved C-terminal translocation domain inserting into the outer membrane of the bacterial cell, and a variable internal functional passenger domain, which is translocated to the bacterial surface (3)(4)(5). The trimeric autotransporters (TAAs) represent a subfamily of AT proteins and are defined by the presence of a very short C-terminal translocator domain that forms highly stable trimers in the outer membrane (7)(8)(9). All TAA proteins identified to date display bacterial adherence, adhesion, and aggregation activities to mediate bacterial interactions with either host cells or extracellular matrix (ECM) proteins.…”

“…All TAA proteins identified to date display bacterial adherence, adhesion, and aggregation activities to mediate bacterial interactions with either host cells or extracellular matrix (ECM) proteins. The conventional ATs are involved in the adhesion, cytotoxicity, and lipase or protease activities of bacteria (4,7,8,(10)(11)(12)(13)(14)(15).…”