7pdc
The structure of the human tetrameric LL-37 peptide in a channel conformation
Structural highlights
FunctionCAMP_HUMAN Binds to bacterial lipopolysaccharides (LPS), has antibacterial activity.[1] [2] Publication Abstract from PubMedThe 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. The structure of the antimicrobial human cathelicidin LL-37 shows oligomerization and channel formation in the presence of membrane mimics.,Sancho-Vaello E, Gil-Carton D, Francois P, Bonetti EJ, Kreir M, Pothula KR, Kleinekathofer U, Zeth K Sci Rep. 2020 Oct 15;10(1):17356. doi: 10.1038/s41598-020-74401-5. PMID:33060695[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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