PROSITE documentation PDOC00729

Cathelicidins signatures

The precursor sequences of a number of antimicrobial peptides secreted by neutrophils (polymorphonuclear leukocytes) upon activation have been found to be evolutionarily related and are collectively known as cathelicidins [1]. This family includes:

• Pig cathelin, which may be the precursor of an antibacterial peptide.
• Bovine and sheep bactenecin 5 (Bac5) and 7 (Bac7), proline and arginine- rich antibiotics.
• Bovine and sheep cyclic dodecapeptide, a potent antibiotic.
• Bovine indolicidin, a tryptophan-rich potent antibiotic.
• Rabbit CAP18, a protein that binds to the bacterial lipopolysaccharides (LPS) and which also has antibiotic activity.
• Human FALL-39 (or LL-37), an antibacterial LPS-binding peptide.
• Rabbit p15, which also binds to LPS and modulates the antibacterial activity of BPI.
• Pig antibacterial peptide PR-39.
• Bovine myeloid antibacterial peptides BMAP-27 and BMAP-28.
• Pig myeloid antibacterial peptides PMAP-23, PMAP-36 and PMAP-37.
• Pig protegrin-1 to -5.
• Sheep myeloid antibacterial peptide SMAP-29 (SC-5).
• Mouse CRAMP (CLP).

Structurally, these proteins consist of three domains: a signal sequence, a conserved region of about 100 residues that contains four cysteines involved in two disulfide bonds, and a highly divergent C-terminal section of variable size. It is in this C-terminal section that the antibacterial peptides are found; they are proteolytically processed from their precursor by enzymes such as elastase. This structure is shown in the following schematic representation:

   +---+-*******------*******-----------+--------------------+
   |Sig| Propeptide     C  C  C  C      | Antibacterial pep. |
   +---+----------------|--|--|--|------+--------------------+
                        |  |  |  |
                        +--+  +--+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the patterns.

We derived two signature patterns for these proteins; the first one corresponds to the beginning of the conserved region and the second to a central part that contains two of the conserved cysteines.