Human antimicrobial peptides and proteins

Research output: Contribution to journalReview article

176 Citations (Scopus)

Abstract

As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between -3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.

Original languageEnglish (US)
Pages (from-to)545-594
Number of pages50
JournalPharmaceuticals
Volume7
Issue number5
DOIs
StatePublished - May 13 2014

Fingerprint

Peptides
Proteins
Defensins
Cell Wall
Histatins
C-Type Lectins
Bacteria
Vitamin B Complex
Cyclic Peptides
Perforin
Precision Medicine
Membranes
Peptidoglycan
Volatile Fatty Acids
Isoleucine
Ultraviolet Rays
Muramidase
Ion Channels
Innate Immunity
Vitamin D

Keywords

  • Antimicrobial chemokines
  • Antimicrobial neuropeptides
  • Antimicrobial proteins
  • Cathelicidin ll-37
  • Defensins
  • Dermcidin
  • Hepcidins
  • Histatins
  • Rnases

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Human antimicrobial peptides and proteins. / Wang, Guangshun.

In: Pharmaceuticals, Vol. 7, No. 5, 13.05.2014, p. 545-594.

Research output: Contribution to journalReview article

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