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.
Highlights
Host defense antimicrobial peptides (AMPs) are key components of the innate immune system shared by both invertebrates and vertebrates
HBD-2 was identified from lesional psoriatic skin using the whole E. coli affinity column [32]. This material was selected for AMP isolation based on the fact that patients with lesional psoriatic skin have fewer skin infections than expected. This peptide is effective in killing Gram-negative bacteria E. coli, P. aeruginosa, and yeast C. albicans, but is only bacteriostatic against Gram-positive S. aureus
We highlight atomic structures of human AMPs from the α, β, and αβ families. These structures are annotated in the Antimicrobial Peptide Database (APD) database [8] and structural coordinates can be obtained from the Protein Data Bank (PDB) [202] via the APD links
Summary
Host defense antimicrobial peptides (AMPs) are key components of the innate immune system shared by both invertebrates and vertebrates. They have been identified in a variety of exposed tissues or surfaces such as skin, eyes, ears, mouth, airways, lung, intestines, and the urinary tract. It is recognized that certain defensins play a critical role in sperm fertilization [17,18,19] By the time this manuscript was completed, 103 human AMPs were found in the APD [7,8]. The lengths of these human peptides range from 10 (neurokinin A) to 149 amino acids (RegIIIα) ELTEAQRRGLQVALEEFHKHP skin PVQWAFQETSVESAVDTPFPA GIFVRLEFKLQQTSCRKRDWK KPECKVRPNGRKRKCLACIKL GSEDKVLGRLVHCPIETQVLR EAEEHQETQCLRVQRAGEDP HSFYFPGQFAFS [49]
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