LL-37 is the best-known example of a human host-defense peptide, and it carries its length in its name. This profile covers where it comes from in the cell, how it was discovered, and why results with it depend heavily on how a lab runs the assay.
What LL-37 Is
LL-37 is a 37-residue cationic peptide released from a larger precursor protein called hCAP-18. The name comes from its two N-terminal leucines and its length. It belongs to the cathelicidin family, which Sørensen and colleagues (2001) describe as antimicrobial proteins stored in neutrophil granules, and notes that hCAP-18 is the only cathelicidin in humans.
| Property | Value |
|---|---|
| Length | 37 residues |
| Sequence (UniProt P49913, residues 134–170) | LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES |
| Approximate mass | about 4.49 kDa (our calculation from the sequence) |
| Precursor | hCAP-18 (human cationic antimicrobial protein, 18 kDa) |
| Family | Cathelicidins |
| Charge | Net positive (cationic) |
How the Peptide Was Found
Two independent groups cloned the gene in 1995.
- Agerberth and colleagues (1995) were looking for a human counterpart to a pig antibiotic peptide and found, in a human bone marrow cDNA library, a clone for a 39-residue peptide they named FALL-39 after its first four residues. They reported that synthetic FALL-39 was active against Escherichia coli and Bacillus megaterium in a basal laboratory medium (medium E) and that part of the sequence could form an amphipathic helix.
- Larrick and colleagues (1995) cloned the same gene from a bone marrow library and named the protein human CAP18, building on a lipopolysaccharide-binding protein first purified from rabbit leukocytes. They characterized the C-terminal 37-residue region, designated CAP18(104–140), and a slightly shorter, more active fragment.
The mature peptide ended up being the 37-residue version, LL-37, rather than the 39-residue FALL-39.
How the Cell Makes It
In 2001, Sørensen and colleagues showed that hCAP-18 is cleaved to LL-37 after the contents of neutrophil granules are released, and that of three azurophil granule serine proteases, proteinase 3 was solely responsible for the cleavage. They noted that this differs from how bovine and porcine cathelicidins are processed, which is a reminder that findings from other species cannot be assumed to transfer.
What In-Vitro Studies Have Examined
- Antimicrobial assays. The original 1995 papers measured activity against bacteria in culture.
- Cytotoxicity. Sørensen and colleagues describe LL-37 as both antibacterial and cytotoxic, which means assays should include cell viability controls.
- Structure. The 1995 work showed the peptide has a stretch that can form an amphipathic helix, and that helix formation depended on the medium.
These are cell culture and test-tube studies. They are not evidence of any effect in people.
Why Assay Conditions Matter
The first FALL-39 paper reported activity in a defined basal medium and measured helix content in the same medium. A cationic, helix-forming peptide can behave differently in different salt, serum and pH conditions, and it can adsorb to plastic surfaces. When you read or run an antimicrobial assay with LL-37:
- record the medium, ionic strength and temperature;
- note the container material;
- include controls for cell toxicity if cells are in the system;
- compare your results only with papers that used the same format.
If You Source This Compound for Research
- Check that the report's mass (about 4.49 kDa) corresponds to the 37-residue peptide, not to the 39-residue FALL-39.
- Ask for HPLC purity and the counter-ion form, because the counter-ion can matter in sensitive cell assays.
- Store lyophilized material cold, dry and away from light. See Storing Lyophilized Peptides in the Lab and How to Read a Peptide Analytical Report.
FAQ
Why is it called LL-37? For the two leucines at its start and the 37 residues in the peptide.
Is FALL-39 the same thing? FALL-39 is the 39-residue form predicted from the first cloned sequence. LL-37 is the 37-residue form that was later shown to be generated by cleavage of hCAP-18.
Is LL-37 a protein or a peptide? Both words are used. It is a 37-residue fragment of a larger protein.
Sources
- Agerberth B et al. Proceedings of the National Academy of Sciences, 1995. PubMed 7529412: https://pubmed.ncbi.nlm.nih.gov/7529412/
- Larrick JW et al. Infection and Immunity, 1995. PubMed 7890387: https://pubmed.ncbi.nlm.nih.gov/7890387/
- Sørensen OE et al. Blood, 2001. PubMed 11389039: https://pubmed.ncbi.nlm.nih.gov/11389039/
- UniProt entry P49913 (cathelicidin sequence): https://www.uniprot.org/uniprotkb/P49913
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