Pilin refers to a class of fibrous

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s that are found in

pilus A pilus (Latin for 'hair'; : pili) is a hair-like cell-surface appendage found on many bacteria and archaea. The terms ''pilus'' and '' fimbria'' (Latin for 'fringe'; plural: ''fimbriae'') can be used interchangeably, although some researchers ...

structures in

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

. These structures can be used for the exchange of

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

tic material, or as a

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as Cell_junction, cell junc ...

mechanism. Although not all bacteria have pili or fimbriae, bacterial

pathogen In biology, a pathogen (, "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 Germ theory of d ...

s often use their fimbriae to attach to host cells. In

Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

bacteria, where pili are more common, individual pilin molecules are linked by

noncovalent In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The ...

protein-protein interactions, while

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

bacteria often have

polymer A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...

ized LPXTG pilin.

Type IV pilin

Type IV pilin proteins are α+β proteins characterized by a very long

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

alpha helix An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...

. The assembly of these pili relies on interactions between the N-terminal helices of the individual monomers. The pilus structure sequesters the helices in the center of the fiber lining a central pore, while antiparallel

beta sheet The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...

s occupy the exterior of the fiber.

Role of ComP pilin in bacterial transformation

Genetic transformation In molecular biology and genetics, transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane(s). For transformation to t ...

is the process by which a recipient bacterial cell takes up DNA from a neighboring cell and integrates this DNA into the recipient’s genome by

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...

. In ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as the meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to a ...

'', DNA transformation requires the presence of short

DNA uptake sequence Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

s (DUSs) which are 9-10mers residing in

coding region The coding region of a gene, also known as the coding DNA sequence (CDS), is the portion of a gene's DNA or RNA that codes for a protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared ...

s of the donor DNA. Specific recognition of DUSs is mediated by a type IV pilin, ComP. Menningococcal type IV pili bind DNA through the minor pilin ComP via an electropositive stripe that is predicted to be exposed on the filament's surface. ComP displays an exquisite binding preference for selective DUSs. The distribution of DUSs within the ''N. meningitidis'' genome favors certain genes, suggesting that there is a bias for genes involved in genomic maintenance and repair.

Chaperone-usher pilin

The Cup family is known for its use of a chaperone and at least an usher. They exhibit an Ig fold.

Saf, N-terminal extension

The Saf pilin N-terminal extension

protein domain In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...

helps the pili to form, via a complex mechanism named the chaperone/ usher pathway. It is found in all c-u pilins. This protein domain is very important for such bacteria, as without pili formation, they could not infect the host. Saf is a ''Salmonella''

operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

containing a c-u pilus system.

Function

This protein domain, has an important function in forming pili. These are virulence factors crucial for

to the host and

biofilm A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...

formation with successful infection.

Structure

This

consists of the adjacent Saf-Nte and Saf-pilin

chain A chain is a serial assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a rope in that it is flexible and curved in compression but linear, rigid, and load-bearing in tension. A ...

s of the pilus-forming

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

. They are Chaperone/usher (CU) pili, and have an

extension (Nte) of around 10-20

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. Salmonella Saf pili, which are assembled by FGl chaperones. The structure has been well conserved, as they contain a set of alternating

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

residues that form an essential part of the subunit–subunit interaction.

Mechanism

The mechanism for the assembly reaction is termed donor strand exchange DSE which

Pilus A pilus (Latin for 'hair'; : pili) is a hair-like cell-surface appendage found on many bacteria and archaea. The terms ''pilus'' and '' fimbria'' (Latin for 'fringe'; plural: ''fimbriae'') can be used interchangeably, although some researchers ...

assembly in Gram-negative

involves a Donor-strand exchange

mechanism Mechanism may refer to: *Mechanism (economics), a set of rules for a game designed to achieve a certain outcome **Mechanism design, the study of such mechanisms *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a ...

between the C- and the N-termini of this domain. The C-terminal subunit forms an incomplete Ig-fold which is then complemented by the 10-18 residue N terminus of another. The N terminus

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...

s contain a motif of alternating

residues that occupy the P2 to P5 binding pockets in the groove of the first pilus subunit.

LPXTG pilin

LPXTG pilin is common in

gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

cocci. They are named for a C-terminal motif used by the

sortase Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-an ...

. There is also a LPXTGase.

Development of molecular tools

LPXTG Pili in

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain ...

contain spontaneously formed

isopeptide bond An isopeptide bond is a type of amide bond formed between a carboxyl group of one amino acid and an amino group of another. An isopeptide bond is the linkage between the side chain amino or carboxyl group of one amino acid to the α-carboxyl, α- ...

s. These bonds provide enhanced mechanical and proteolytic stability to the pilin protein. Recently, the pilin protein from ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'' has been split into two fragments to develop a new molecular tool called the isopeptag. The isopeptag is a short peptide that can be attached to a protein of interest and can bind its binding partner through a spontaneously formed

. This new peptide tag can allow scientists to target and isolate their proteins of interest through a permanent

covalent bond A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...