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Cited by 184Antimicrobial Peptides and ActivitiesAntimicrobial agents and applicationsProtein Structure and Dynamics

High‐quality 3D structures shine light on antibacterial, anti‐biofilm and antiviral activities of human cathelicidin LL‐37 and its fragments

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Wang, Guangshun, Mishra, Biswajit, Epand, Raquel F., Epand, Richard M.·2014·Biochimica et Biophysica Acta (BBA) - Biomembranes
DOI 10.1016/j.bbamem.2014.01.016PMC PMC4082733
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Abstract

Host defense antimicrobial peptides are key components of human innate immunity that plays an indispensible role in human health. While there are multiple copies of cathelicidin genes in horses, cattle, pigs, and sheep, only one cathelicidin gene is found in humans. Interestingly, this single cathelicidin gene can be processed into different forms of antimicrobial peptides. LL-37, the most commonly studied form, is not only antimicrobial but also possesses other functional roles such as chemotaxis, apoptosis, wound healing, immune modulation, and cancer metastasis. This article reviews recent advances made in structural and biophysical studies of human LL-37 and its fragments, which serve as a basis to understand their antibacterial, anti-biofilm and antiviral activities. High-quality structures were made possible by using improved 2D NMR methods for peptide fragments and 3D NMR spectroscopy for intact LL-37. The two hydrophobic domains in the long amphipathic helix (residues 2-31) of LL-37 separated by a hydrophilic residue serine 9 explain its cooperative binding to bacterial lipopolysaccharides (LPS). Both aromatic rings (F5, F6, F17, and F27) and interfacial basic amino acids of LL-37 directly interact with anionic phosphatidylglycerols (PG). Although the peptide sequences reported in the literature vary slightly, there is a consensus that the central helix of LL-37 is essential for disrupting superbugs (e.g., MRSA), bacterial biofilms, and viruses such as human immunodeficiency virus 1 (HIV-1) and respiratory syncytial virus (RSV). In the central helix, the central arginine R23 is of particular importance in binding to bacterial membranes or DNA. Mapping the functional roles of the cationic amino acids of the major antimicrobial region of LL-37 provides a basis for designing antimicrobial peptides with desired properties. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.

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Cited by

Sorted by citations

Authors
Wang, G., Mishra, B., Epand, R. F., & Epand, R. M.
Affiliations
  • Nebraska Medical Center (US)
  • McMaster University (CA)
Corresponding author
Wang, Guangshun
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - Biomembranes
Publisher
Elsevier BV
Published
2014-09
Volume
1838
Issue
9
Pages
2160-2172
ISSN
0005-2736 (ISSN-L)
DOI
10.1016/j.bbamem.2014.01.016
PMC
PMC4082733
OpenAlex
W2144286887
Cited by
184
References
3
Citations by year
2026: 10 · 2025: 10 · 2024: 15 · 2023: 15 · 2022: 11 · 2021: 13 · 2020: 18 · 2019: 13 · 2018: 13 · 2017: 17 · 2016: 26 · 2015: 19 · 2014: 4
FWCI
3.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochimica et Biophysica Acta (BBA) - Biomembranes (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIAID
  • NIH (1R56AI105147-01)
  • State of Nebraska Research Initiative
  • Natural Sciences and Engineering Research Council (9848)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
LL-37, cathelicidin, antimicrobial peptides, peptide structure, antibacterial activity, antibiofilm activity, antiviral activity, HIV-1, respiratory syncytial virus, lipopolysaccharide binding, methicillin-resistant Staphylococcus aureus, peptide fragments
MeSH terms
Antiviral Agents, Cell Membrane, Cell Membrane Permeability, Humans, Lipid Bilayers, Protein Conformation, Biofilms, Nuclear Magnetic Resonance, Biomolecular, Antimicrobial Cationic Peptides, Cathelicidins

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