Human Antimicrobial Peptides and Proteins

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.

Deciphering the tRNA-dependent lipid aminoacylation systems in bacteria: Novel components and structural advances

“…It is proposed that the high diversity of structure and function among eukaryotic CAMPs has been shaped by a variety of crosstalk between host cells and bacterial species. 11,12 The diversity of CAMPs in eukaryotes is illustrated in the Antimicrobial Peptide Database, 13 which lists more than 2,500 CAMPs of eukaryotic origin (122 in human 14 ) and only 301 CAMPs of prokaryotic origin (only four were identified in archae). In mammals, CAMPs are produced and secreted by epithelial cells ( i.e.…”

Anti-Staphylococcal Biofilm Effects of Human Cathelicidin Peptides

“…5 The major AMPs in humans are cathelicidins, defensins, dermcidins, hepcidins, RNases, and histatins. 6 Human cathelicidin LL-37 is a wellstudied AMP with activity against bacteria, viruses, fungi, and parasites. In addition, LL-37 can regulate immune response, wound healing, and apoptosis.…”

Antimicrobial Proteins and Their Importance in Immunity

“…HNP-1,2,3, defensinler, LL-37 ve granülisinin antikanser etkilerinin olduğu gösterilmi ştir. Kanser hastalığı sırasında granülizin ekspresyonu artmaktadır 12 . 25,26 .…”