CFP-10 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

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that is encoded by the esxB gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

CFP-10 is a 10 kDa secreted antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 from Mycobacterium tuberculosis

Mycobacterium tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. It forms a 1:1 heterodimeric complex with ESAT-6

ESAT-6

ESAT-6, the 6 kDa early secretory antigenic target of Mycobacterium tuberculosis, 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, in conjunction with CFP-10 and TB7.7.ESAT-6 has been shown to directly...

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

Genome

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 and play a key role in the virulence

Virulence

Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 of the infection.

Function

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

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 that contributes to the virulence Mycobacterium tuberculosis

Mycobacterium tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

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

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 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. The RD1 region is genomic and is present in all strains of Mycobacterium tuberculosis

Mycobacterium tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. Mycobacterium tuberculosis uses this ESX-1 secretion system to deliver virulence factors into host macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

 and monocyte

Monocyte

Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...

 white blood cells during infection.
In Mycobacterium tuberculosis

Mycobacterium tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

, 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 Mycobacterium tuberculosis

Mycobacterium tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. ^[4].

Structure

The 10-kDa culture filtrate protein (CFP-10) and 6kDaA early secreted antigen target (ESAT-6) complex is a 100 amino-acid 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 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.