The structure of the antimicrobial human cathelicidin LL-37 shows oligomerization and channel formation in the presence of membrane mimics.
Sancho-Vaello. Enea E; Gil-Carton. David D; François. Patrice P; Bonetti. Eve-Julie EJ; Kreir. Mohamed M; Pothula. Karunakar Reddy KR; Kleinekathöfer. Ulrich U; Zeth. Kornelius K
Key Findings
- LL-37 forms a tetrameric channel in membrane‑like environments
- The channel shows measurable conductivity and lets water move through
- Channel formation leads to bacterial outer‑membrane damage and cell death
- Structural data can guide design of more potent LL-37 derivatives
Practical Outcomes
- Knowing LL-37’s channel‑forming action suggests you could look for or develop LL-37‑based products that are more effective at killing bacteria. For now, it mainly informs future supplement or topical formulation design rather than giving a specific dosage or protocol.
Summary
Scientists discovered that the human antimicrobial peptide LL-37 can group together into a four‑unit channel that punches holes in bacterial membranes, letting water and ions pass and killing the bugs. This structural insight helps explain how LL-37 works and points to ways to make stronger versions.
Abstract
The human cathelicidin LL-37 serves a critical role in the innate immune system defending bacterial infections. LL-37 can interact with molecules of the cell wall and perforate cytoplasmic membranes resulting in bacterial cell death. To test the interactions of LL-37 and bacterial cell wall components we crystallized LL-37 in the presence of detergents and obtained the structure of a narrow tetrameric channel with a strongly charged core. The formation of a tetramer was further studied by cross-linking in the presence of detergents and lipids. Using planar lipid membranes a small but defined conductivity of this channel could be demonstrated. Molecular dynamic simulations underline the stability of this channel in membranes and demonstrate pathways for the passage of water molecules. Time lapse studies of E. coli cells treated with LL-37 show membrane discontinuities in the outer membrane followed by cell wall damage and cell death. Collectively, our results open a venue to the understanding of a novel AMP killing mechanism and allows the rational design of LL-37 derivatives with enhanced bactericidal activity.
Study Information
pubmed
2020
2020-10-15T00:00:00.000Z
10.1038/s41598-020-74401-5
93
108