6S6M

Crystal structure of the human LL37(17-29) antimicrobial peptide

Summary for 6S6M

• Entry DOI: 10.2210/pdb6s6m/pdb
• Descriptor: Cathelicidin antimicrobial peptide (2 entities in total)
• Functional Keywords: helical and tubular fibril structure of a human derived antimicrobial peptide, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 3448.25

Authors

Landau, M.,Engelberg, Y. (deposition date: 2019-07-03, release date: 2020-08-19, Last modification date: 2024-05-15)

Primary citation

Engelberg, Y.,Landau, M.
The Human LL-37(17-29) antimicrobial peptide reveals a functional supramolecular structure.
Nat Commun, 11:3894-3894, 2020

PubMed Abstract: Here, we demonstrate the self-assembly of the antimicrobial human LL-37 active core (residues 17-29) into a protein fibril of densely packed helices. The surface of the fibril encompasses alternating hydrophobic and positively charged zigzagged belts, which likely underlie interactions with and subsequent disruption of negatively charged lipid bilayers, such as bacterial membranes. LL-37 correspondingly forms wide, ribbon-like, thermostable fibrils in solution, which co-localize with bacterial cells. Structure-guided mutagenesis analyses supports the role of self-assembly in antibacterial activity. LL-37 resembles, in sequence and in the ability to form amphipathic helical fibrils, the bacterial cytotoxic PSMα3 peptide that assembles into cross-α amyloid fibrils. This argues helical, self-assembling, basic building blocks across kingdoms of life and points to potential structural mimicry mechanisms. The findings expose a protein fibril which performs a biological activity, and offer a scaffold for functional and durable biomaterials for a wide range of medical and technological applications.

PubMed: 32753597
DOI: 10.1038/s41467-020-17736-x

Experimental method

X-RAY DIFFRACTION (1.35 Å)