CFP-10 within

bacterial proteins 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 ...

(also known as ESAT-6-like protein esxB or secreted antigenic protein MTSA-10 or 10 kDa culture filtrate antigen CFP-10) is a

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 ...

that is encoded by the ''esxB''

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 ...

. CFP-10 is a 10 kDa secreted

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

from ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...

''. It forms a 1:1

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

ic complex with

ESAT-6 ESAT-6 or Early Secreted Antigenic Target 6 kDa, is produced by ''Mycobacterium tuberculosis'', it is a secretory protein and potent T cell antigen. It is used in tuberculosis diagnosis by the whole blood interferon γ test QuantiFERON-TB Gold, i ...

. Both genes are expressed from the RD1 region of the bacterial

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

and play a key role in the

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 ca ...

of the infection.

Function

10-kDa culture filtrate protein (CFP-10) is an

that contributes to the virulence

. CFP-10 forms a tight 1:1 heterodimeric complex with 6kDaA early secreted

target (ESAT-6). In the mycobacterial cell, these two proteins are interdependent on each other for stability. The ESAT-6/CFP-10 complex is secreted by the ESX-1 secretion system, also known as the RD1 region. Mycobacterium tuberculosis uses this ESX-1 secretion system to deliver virulence factors into host

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

and

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

white blood cells during infection. In

, the core components of the whole ESX-1 secretion system include Rv3877, and two AAA ATPases, including Rv3870 and Rv3871, a cytosolic protein. The ESAT-6/CFP-10 heterodimer complex is targeted for secretion by a C-terminal signal sequence on CFP-10 that is recognized by the cytosolic Rv3871 protein. Rv3871 then interacts with the CFP-10 C-terminal, and escorts the ESAT-6/CFP-10 complex to Rv3870 and Rv3877, a multi-transmembrane protein which makes up the pore that spans the cytosolic membrane of the virulent host cell. Once ESAT-6/CFP-10 is next to the membrane of the virulent host cell, the CFP-10 C-terminal attaches and binds itself to the cells surface. The ESAT-6/CFP-10 complex’s secretion and attachment to the virulent host cell shows its contribution to the pathogenicity of

. ^{/sup>.

Structure

The 10-kDa culture filtrate protein (CFP-10) and 6kDaA early secreted antigen target (ESAT-6) complex is a 100 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 ami ...
sequence protein. ESAT-6/CFP-10 has a hydrophobic nature as well as a high content of α-helical structures. Resonance structure analysis of the complex reveals two similar helix-turn-helix hairpin structures formed by the individual proteins, which lie anti-parallel to each other and forms a four-helix bundle. Its long flexible arm projecting off the four-helix bundle, formed by the seven 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 ami ...
C-terminal of CFP-10, is essential for binding and attaching to the surface of host white blood cells; such as macrophages and monocytes. If this C-terminus is cleaved off, the complex shows greatly reduced attachment ability.

See also

* QuantiFERON

Interferon-gamma release assays (IGRAs) are diagnostic tools for latent tuberculosis infection (LTBI). They are surrogate markers of ''Mycobacterium tuberculosis'' infection and indicate a cellular immune response to ''M. tuberculosis'' if the lat ...

* ESAT-6

ESAT-6 or Early Secreted Antigenic Target 6 kDa, is produced by ''Mycobacterium tuberculosis'', it is a secretory protein and potent T cell antigen. It is used in tuberculosis diagnosis by the whole blood interferon γ test QuantiFERON-TB Gold, i ...

References

Further reading

*
{{refend

Tuberculosis
Bacterial proteins}