LL-37 (Human Cathelicidin) vs MOTS-c

LL-37 (Human Cathelicidin)

LL-37 is a 37-residue peptide cleaved from hCAP18, the only human cathelicidin; its name refers to its two leading leucines and its length. It is made by neutrophils and by epithelial cells of the skin, gut and airways, and the gene that encodes it is regulated in part by vitamin D. Laboratory studies have examined its activity against bacteria, fungi and some viruses, and its signalling to host immune and epithelial cells. Its research record runs in two directions: it is studied as a host-defence molecule and also as a contributor to inflammatory skin conditions such as psoriasis and rosacea. Most published work is in vitro or in animals, and interventional human studies are few and small.

MOTS-c

MOTS-c is a 16-residue peptide encoded by a short open reading frame within the mitochondrial gene for 12S ribosomal RNA. It belongs to the mitochondrial-derived peptides, a small group that also includes humanin, which is encoded in the 16S rRNA gene. Since it was first described in the mid-2010s it has been studied mainly in cultured cells and in mice, with attention to glucose and lipid handling in skeletal muscle and to cellular responses to metabolic stress. Human data are limited and consist mostly of measurements of its circulating levels in observational studies.

How LL-37 (Human Cathelicidin) acts

In dilute aqueous solution LL-37 is largely disordered; on contact with lipid membranes it has been reported to fold into an amphipathic α-helix. Its side chains give it a net charge of about +6 at neutral pH, which draws it to the negatively charged surfaces of bacterial membranes, and it is thought to permeabilise those membranes. It also binds bacterial lipopolysaccharide. On host cells it has been reported to act through several receptors, among them formyl peptide receptor 2 and the P2X7 purinergic receptor, and to transactivate the epidermal growth factor receptor in keratinocytes. Complexes of LL-37 with self-DNA or RNA have been reported to activate Toll-like receptor signalling in dendritic cells, a pathway examined in psoriasis research.

How MOTS-c acts

The first cell and mouse studies reported that MOTS-c inhibits the folate pathway and, with it, de novo purine synthesis, so that the purine intermediate AICAR accumulates. This nucleotide mimics AMP and activates AMP-activated protein kinase (AMPK), a sensor of cellular energy status. Later work reported that under metabolic or oxidative stress the peptide moves from the cytoplasm into the nucleus, where it associates with transcription factors including NRF2 and alters the expression of stress-response genes. Most of this mechanistic evidence comes from cell and rodent models, and human mechanistic data are scarce.

The records side by side

• Type: LL-37 (Human Cathelicidin), Antimicrobial peptide (cathelicidin); MOTS-c, Mitochondrial-derived peptide (MDP)
• Length: LL-37 (Human Cathelicidin), 37 amino acids; MOTS-c, 16 amino acids
• Molecular weight: LL-37 (Human Cathelicidin), 4493 g/mol; MOTS-c, 2174.6 g/mol
• Molecular formula: LL-37 (Human Cathelicidin), C205H340N60O53; MOTS-c, C101H152N28O22S2

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.