LL-37

LL-37 is the thirty-seven-residue mature antimicrobial peptide released from human cathelicidin, the product of the CAMP gene. UniProt P49913 annotates it as residues 134 to 170 of the 170-residue precursor.

The name records the sequence: it begins with two leucines and runs thirty-seven residues to a C-terminal serine, carried as the free acid with a free N-terminal amine. There is no acetylation and no amidation. One distinction matters for anyone matching a mass against a label. FALL-39, the thirty-nine-residue species Agerberth and colleagues predicted in 1995, begins two residues earlier at Phe132; the peptide processed in granulocytes and described by Gudmundsson and colleagues in 1996 is the thirty-seven-residue form supplied here, and the two have different masses.

There is no cysteine in the sequence, which Agerberth and colleagues stated in their title, and the two disulfides recorded on UniProt P49913 at residues 86 to 97 and 108 to 125 belong to the cathelin-like propeptide rather than to this fragment. Carrying those bonds onto a specification for LL-37 is a common transcription error and they are absent here for that reason.

The molecule has four phenylalanines, at positions 5, 6, 17 and 27, and no tryptophan or tyrosine at all. Phenylalanine absorbs near 257 nm and contributes essentially nothing at 280 nm, so absorbance at 280 nm cannot be used to determine concentration here; amino-acid analysis, low-ultraviolet absorbance or quantitative NMR is required instead.

Structurally it is a curved amphipathic helix. Solution NMR in detergent micelles, deposited as PDB 2K6O by Wang in 2008, resolves a helix-bend-helix spanning residues 2 to 31 with the bend between Gly14 and Glu16 and a disordered C-terminal tail; those same four phenylalanine rings make the lipid contacts. A 1.9 Angstrom crystal structure from Sancho-Vaello and colleagues, PDB 5NNM, shows the dimer.

Its best-characterised molecular partner is not a protein but the anionic lipid bilayer itself. The clearest protein receptor in the literature is FPR2, the N-formyl peptide receptor 2 (UniProt P25090), a class A G-protein-coupled receptor; Yang and colleagues reported calcium mobilisation in receptor-transfected HEK293 cells in 2000. Other reported interactors rest on single reports and are not treated here as established.

Two things frequently quoted for this peptide are not supported by a primary source and are left out: a quantitative figure for adsorptive loss to glass or plastic, and any documented forced-degradation pathway. FDA GSRS also carries a molecular-formula text field for this substance that is chemically impossible, so the formula above is taken from PubChem CID 16198951, which agrees with the sequence.