Structural Plasticity of LL-37 Indicates Elaborate Functional Adaptation Mechanisms to Bacterial Target Structures

Area of Science:

• Immunology
• Structural Biology
• Antimicrobial Peptides

Background:

• The human cathelicidin LL-37 is a key component of the innate immune system.
• LL-37 possesses broad antimicrobial activity against various microorganisms.
• Its known targets include bacterial membrane lipids, lipopolysaccharides (LPS), and lipoteichoic acid (LTA).

Purpose of the Study:

• To review LL-37 structural data from the past 15 years.
• To discuss structural features involved in LL-37 interactions with lipid-like molecules.
• To understand LL-37's conformational and oligomeric adaptability.

Main Methods:

• Analysis of existing structural data of LL-37.
• Discussion of LL-37 structures determined with membrane-mimicking detergents.
• Examination of co-crystal structures of LL-37 with detergents.

Main Results:

• LL-37 exhibits diverse structures, including monomers, dimers, tetramers, and fibers.
• Detergent-mimicking lipids and LPS reveal LL-37's oligomerization and fibrillation.
• Conserved phenylalanine and arginine residues are crucial for lipid and LPS interactions.

Conclusions:

• LL-37's structural plasticity is essential for its broad antimicrobial targeting.
• Detergent complex structures offer insights into lipid-mimicking interactions.
• Further studies on LL-37 complexes with proteins and DNA are needed for rational drug design.