In molecular biology, YadA is a

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of ...

which is short for ''Yersinia'' adhesin A. These proteins have strong sequence and structural homology, particularly at their

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

end. The function is to promote their

pathogenicity In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ge ...

and

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...

in host cells, though cell adhesion. YadA is found in three pathogenic species of ''Yersinia'', ''Y. pestis,'' ''Y. pseudotuberculosis'', and ''Y. enterocolitica''. The YadA domain is encoded for by a virulence plasmid in ''Yersinia'', which encodes a type-III secretion (T3S) system consisting of the Ysc injectisome and the Yop effectors.

Function

Essentially, the main function of the YadA domain is to help cell adhesion and to increase

. YadA is a collagen-binding outer membrane protein. It forms the fibrillar matrix on the bacterial cell surface. This aids cell attachment and helps the

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...

invade

eukaryotic Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...

cells. Additionally, by forming the fibrillar matrix, the YadA domain protects the bacteria by facilitating

agglutination In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...

resistance, serum resistance, complement inactivation and

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...

resistance. The importance of adhesins to YadA function and ''Yersinia'' survival is huge. Attachment further allows more interactions and increase of

biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...

formation to aid bacterial colonization. In ''Yersinia'', it helps initiate the infectious process in host cells and are critical virulence factors. Additionally, bacteria have the ability to regulate adhesion expression, meaning that when ''Yersinia'' no longer requires YadA, it can be turned off. Furthermore, YadA expression is mainly temperature regulated, at 37 degrees Celsius. It also has two molecular regulators: an activator, VirF and a repressor, YmoA.

Substrate adhesion

The YadA protein domain adheres to the following substrates: *

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...

* collagen * cellular

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...

Protein domains in YadA

C terminal domain

The

domain consists of 120

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

s which belong to a family of surface-exposed

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s. The YadA C-terminal domain has a particular function in translocating the trimeric N-terminal passenger domain to the exterior of the membrane and is also responsible for trimerisation.

Structure

C-terminal domain structure

The C-terminal region is a

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

region which consists of 4 beta strands which form trimers in the outer membrane. The C-terminal contains 9 amino acids which alternate

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

amino acids ending in F ( Phenylalanine) or W (

Tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

), this composes a targeting motif for the outer membrane of the

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

. This region is important for

oligomerisation In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...

. The C-terminal domain helps to build the beta barrel pore in the outer membrane.

YadA protein structure

YadA is a homotrimeric outer membrane protein which forms part of the fibrillar matrix. Simplistically, this means the protein is made of three of the same subunits, on the outer surface of the membrane. The surface is entirely covered in the YadA lollipop structures. made of a short

membrane anchor, an 18 nm long coiled-coil stem and a 5 nm long N-terminal globular head structure consisting of a left-handed parallel beta roll. YadA is an example of an oligomeric coiled-coil adhesion (Oca). The Oca protein families are a subset of autotransporters, also known as the type Vc or trimeric autotransporters. Trimerization is thought to involve the coiled-coil stem and the C-terminal membrane anchor, which forms a 12-strand

beta-barrel In protein structures, a beta barrel is a beta sheet composed of tandem repeats that twists and coils to form a closed toroidal structure in which the first strand is bonded to the last strand (hydrogen bond). Beta-strands in many beta-barrels are ...

from the four transmembrane beta-strands of the three monomers. This beta-barrel would form a pore-like structure through which the N-terminal head and coiled helical domains of the three monomer chains exit to the cell surface. The YadA protein domain, is a form of trimeric autotransporter adhesins (TAAs). Each TAA must consist of a head, stalk and a

membrane anchor.

History

YadA, an adhesin from ''

Yersinia ''Yersinia'' is a genus of bacteria in the family Yersiniaceae. ''Yersinia'' species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of ''Yer ...

'', was the first member of this family to be characterised. UspA2 from ''

Moraxella ''Moraxella'' is a genus of gram-negative bacteria in the family Moraxellaceae. It is named after the Swiss ophthalmologist Victor Morax. The organisms are short rods, coccobacilli, or as in the case of ''Moraxella catarrhalis'', diplococci ...

'' was second. The Eib immunoglobulin-binding

s from ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' were third, followed by the DsrA proteins of ''Haemophilus ducreyi'', amongst others.

References

Protein domains Protein families Virulence factors Bacterial proteins {{portal bar, Biology