Trimeric autotransporter adhesin

In molecular biology, trimeric autotransporter adhesins (TAAs), are proteins found on the outer membrane of Gram-negative bacteria. Bacteria use TAAs in order to infect their host cells via a process called cell adhesion. TAAs also go by another name, oligomeric coiled-coil adhesins, which is shortened to OCAs. In essence, they are virulence factors, factors that make the bacteria harmful and infective to the host organism. TAAs are just one of many methods bacteria use to infect their hosts, infection resulting in diseases such as pneumonia, sepsis, and meningitis. Most bacteria infect their host through a method named the secretion pathway. TAAs are part of the secretion pathway, to be more specific the type Vc secretion system. Trimeric autotransporter adhesins have a unique structure. The structure they hold is crucial to their function. They all appear to have a head-stalk-anchor structure. Each TAA is made up of three identical proteins, hence the name trimeric. Once the membrane anchor has been inserted into the outer membrane, the passenger domain passes through it into the host extracellular environment autonomously, hence the description of autotransporter. The head domain, once assembled, then adheres to an element of the host extracellular matrix, for example, collagen, fibronectin, etc.

Molecular structure Most TAAs have a similar protein structure. When observed with electron microscopy, the structure has been described as a "lollipop" shape consisting of an N-terminal head domain, a stalk domain, and a C-terminal membrane anchor domain. Often, the literature refers to these as Passenger domain, containing the N-terminal, head, neck, and coiled-coil stalk, and the Translocation domain, referring to the C-terminal membrane anchor. Although all TAAs carry a membrane anchor in common, they may not all contain both a stalk and a head as well. In addition, all membrane anchor domains are of the left-handed parallel beta-roll type.

Extended Signal Peptide Region domain

The Extended Signal Peptide Region (ESPR) is found in the N-terminus of the signal peptides of proteins belonging to the Type V secretion systems. The function of the ESPR is to aid inner membrane translocation by acting as a temporary tether. This prevents the accumulation of misfolded proteins. The ESPR can be divided into individual regions, they are as follows: N1 (charged), H1 (hydrophobic), N2, H2 and C (cleavage site) domains. N1 and H1 form the ESPR and have strong conservation. Function: There are several roles that the Extended Signal Peptide Region is thought to hold. First, biogenesis of proteins in the Type V Secretion System (T5SS). Second, it is thought to target the protein to the inner membrane to be translocated either by the signal recognition particle pathway (SRP) or by twin arginine translocated (TAT). Third, it has been observed and believed to regulate the rate of protein migration into the periplasm.

N-terminal head domain Structure: This particular domain is a trimer of single-stranded, left-handed beta-helices. These associate to form a nine-coiled left-handed beta-roll. It contains sequence motifs, of which there is a strong similarity with other TAA heads. This indicates that there is a lot of similarity when comparing protein structure. The head domain is connected to the stalk by a short, highly conserved sequence, which is often called the neck, or occasionally named the connector. Function: The function of this protein domain is to bind to the extracellular matrix of the host, most notably fibronectin, collagen, and laminin. The head domain is very important for attachment to the host cell and for autoagglutination, sticking to itself.

There are several types of head domain. Each domain helps the head to bind to a different component of the extracellular matrix. These are as follows: YadA-like head domain, Trp-ring, GIN, FxG, HIN1, and HIN2. This entry focuses on the first three mentioned.

YadA-like head YadA-like head is composed of single-stranded, left-handed beta-helices, which associate further to create a nine-coiled left-handed parallel beta-roll (LPBR). It is the tightest beta-roll structure known, and the first to be discovered. The YadA head domain has eight repeat motifs, each fourteen residues in length.

Trp ring The Trp ring is the second-most-common TAA head. Trp is an amino acid named tryptophan. The Trp ring obtains its name from the high levels of tryptophan found in the C-terminal part of the Head domain. These work by stabilising the transition between the coiled-coil and the beta-meander where the head meets the neck or stalk. In many cases, the Trp ring is often followed by the GIN domain.

GIN The GIN domain is a head domain named after its sequence motif GIN (Glycine-Isoleucine-Asparagine) motif. It has an all-beta structure, whereby the two pairs of antiparallel beta sheets are connected by a diagonally running extended beta-sheet. The sheets then further fold to form a beta prism in which each wall is composed of a complete set of five beta-strands. The GIN domain is often followed by a neck domain.

Neck domain Structure: The neck domain is a homotrimer, where three of the same subunits associate. All three subunits are arranged in such a way that they resemble a "safety pin"-like structure. Function: The function of the neck domain is to be the adaptor between the larger diameter of the beta-helices and the smaller one of the coiled coil. Furthermore, just like its safety pin structure, it also has a function of pinning all three monomers together and pins it to the head domain. This increases the stability of the neck domain. There are seven different type of neck domains. They are as follows: ISneck1, ISneck2, HANS connector, DALL-1, DALL-2, DALL-3, and the neck domain. This entry focuses on the ISneck domain.

ISneck domain The ISneck domain is a type of neck domain. There are two types of ISneck domain. This first is an ISneck which is interrupted by an insertion. The insertion can take form of either folded (ISneck 1) or much shorter, unfolded (ISneck 2) perturbation.

Stalk domain

Structure: These domains are fibrous and found in highly repetitive numbers. They contain coiled coils and their length tends to vary among different species. The coiled-coil segments of the stalk domains have two unusual properties:

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