Pilin refers to a class of fibrous

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, respo ...

s that are found in

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

structures in

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

. These structures can be used for the exchange of

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

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 junctions or indir ...

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

pathogen 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 germ ...

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

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 wall ...

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 c ...

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. Gram-positive bacte ...

bacteria often have

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

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 ami ...

alpha helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

. 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 g ...

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 ta ...

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 cellular organisms but may ...

. In ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as 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 as a ...

'', DNA transformation requires the presence of short

DNA uptake sequence Uptake signal sequences (USS) are short DNA sequences preferentially taken up by competent bacteria of the family Pasteurellaceae (''e.g.'', ''Haemophilus influenzae''). Similar sequences, called DNA uptake sequences (DUS), are found in species of t ...

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

coding region The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to no ...

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 Usher may refer to: Several jobs which originally involved directing people and ensuring people are in the correct place: * Usher (occupation) ** Church usher ** Wedding usher, one of the male attendants to the groom in a wedding ceremony ** Fiel ...

. 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 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 s ...

helps the pili to form, via a complex mechanism named the chaperone/

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 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 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 c ...

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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

. 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 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, th ...

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

assembly in Gram-negative

involves a Donor-strand exchange

mechanism Mechanism may refer to: *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission *Mechanism (biology), explaining how a feature is created *Mechanism (philosophy), a theory that 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 Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

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 calle ...

s contain a motif of alternating

s 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. Gram-positive bacte ...

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-any ...

. There is also a

LPXTGase LPXTGase refers to an endopeptidase enzyme from Streptococci and Staphylococci with the capacity to cleave the carboxy-terminal LPXTG anchor motif of surface proteins similar to Sortase. However, LPXTGase differs significantly from Sortase in seve ...

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. Gram-positive bact ...

contain spontaneously formed isopeptide bonds. 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 are ...

'' 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 isopeptide bond. 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 atoms ...