Cathelicidin

Cathelicidins are antimicrobial peptides that are produced mainly in immune cells of vertebrates and part of the innate immune response and apoptosis body's own cells. Are transport proteins, their incorporation leads on the one hand to the cell wall of gram-positive bacteria as well as other, in the cell membrane in a loss of ions and small molecules. In man, the CAMP gene is known which codes for two cathelicidins, that are cut from a precursor peptide: FALL -39 and LL -37.

The production of cathelicidin is stimulated in particular by stimulation of TLR -9, as well as TLR -2 and TLR -4 and indirectly through vitamin D.

Vorkommem

Cathelicidins are widely used as antimicrobial peptides in the class (biology) of mammals. Especially numerous and varied they come in the representatives of the group of Cetartiodactyla, which include in particular the Artiodactyla, before. Man has, like most other mammals only a single cathelicidin gene. Outside the class of mammals cathelicidins were only few, such as the domestic fowl, can be detected. Cathelicidin -like peptides were also found in rainbow trout and hagfish. Based on this distribution, the evolution of the historical origin cathelicidins to the period of 500-300 million years ago can be estimated.

Biochemistry

Structure

The structurally heterogeneous family of cathelicidins home to antimicrobial peptides with a length of 12 to 80 amino acid building blocks. The largest group of cathelicidins consists of 23 to 37 -amino acid peptides with an α -helix structure. This group includes the antimicrobial peptides LL -37 and FALL -39 in humans. Another group set which consists of 12 to 18 amino acids, peptides with a β - loop structure that is stabilized by one or two disulfide bridges, dar. Examples include the Protegrins of the pig. A third group of antimicrobial peptides of cathelicidins form consisting of 39-80 amino acids predominantly linear peptides with Polyprolinmotiven. They include, inter alia Bac5 and Bac7 bovine and Prophenine of the pig. A variety of other cathelicidins structure has the bovine indolicidin. Indolicidin is composed of 13 amino acids linear, tryptophan- rich peptide. They all consist of a C -terminal cationic domain that is activated upon cleavage of a holoprotein and is responsible for antimicrobial efficacy.

Biosynthesis

The biosynthesis and activation of cathelicidins is a multistep process. The human cathelicidin LL- 37, encoded by the CAMP gene on chromosome 3. This gene consists, as is the cathelicidin gene of other mammals of four exons. The antimicrobial activity is encoded by the hypervariable exon 4, while the exons 1 to 3 encoding a signal peptide sequence and the subsequent cathelin domain.

Primary prepropeptides be synthesized and stored in the granules of neutrophils or other cells. According to a release of these biologically inactive propeptide they are enzymatically cleaved by elastase or other proteases in a cathelin and a C-terminal antimicrobial peptide.