Human antimicrobial peptides and proteins - PubMed (original) (raw)

Human antimicrobial peptides and proteins

Guangshun Wang. Pharmaceuticals (Basel). 2014.

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Three-dimensional structures of human antimicrobial peptides from the α-helical family: (A) and (B) human cathelicidin LL-37 determined by NMR spectroscopy (PDB ID: 2K6O); (C) dermcidin determined by X-ray crystallography (PDB ID, 2YMK); and (D) granulysin determined by X-ray diffraction (PDB ID: 1L9L). In the case of LL-37, an ensemble of five structures is shown to better view the disordered C-terminal tail (A), whereas a space-filling model is given to show the segregation of the hydrophobic surface (gold) into two domains (B) [182]. The longer one corresponds to the central helix which is important for antimicrobial, anti-biofilm and antiviral activities [83]. Images were generated by using the software MOLMOL [218]. Further details can be found in the text.

Figure 2

Figure 2

Select 3D structures of human antimicrobial peptides from the β and αβ families: (A) HNP-1 (dimeric crystal structure, PDB ID: 3GNY); (B) HD-6 (tetrameric crystal structure, PDB ID: 1ZMQ); (C) hBD-3 (NMR structure, PDB ID: 1KJ6) and RegIIIα (crystal structure, PDB ID: 4MTH). See the text for further details.

Figure 3

Figure 3

3D structures of human chemokines with antimicrobial activity. Shown are (A) CCL1 (NMR structure, PDB ID: 1EL0); (B) CCL8 (crystal structure, PDB ID: 1ESR); (C) CCL11 (NMR structure, PDB ID: 2EOT); (D) CCL21 (NMR structure, PDB ID: 2L4N); (E) CCL27 (NMR structure, PDB ID: 2KUM); (F) CXCL12 (NMR structure, PDB ID: 2KOL); (G) CCL20 (crystal structure, PDB ID: 1M8A); (H) CCL13 (crystal structure, PDB ID: 2RA4); (I) CXCL1 (NMR structure, PDB ID: 1MSH); (J) CXCL10 (crystal structure, PDB ID: 1O80).

Figure 4

Figure 4

3D structures of human ribonucleases with antimicrobial activity. Shown are (A) RNase 3 (dimeric crystal structure, PDB ID: 4A2O); (B) RNase 3 (NMR structure, PDB ID: 2KB5); (C) RNase 5 (crystal structure, PDB ID: 1B1I); (D) RNase 5 (NMR structure, PDB ID: 1AWZ); (E) RNase 2 (crystal structure, PDB ID: 2BZZ); and (F) RNase 7 (NMR structure, PDB ID: 2HKY).

Similar articles

Cited by

References

    1. Boman H.G. Antibacterial peptides: Basic facts and emerging concepts. J. Inter. Med. 2003;254:197–215. doi: 10.1046/j.1365-2796.2003.01228.x. - DOI - PubMed
    1. Ganz T., Lehrer R.I. Defensins. Curr. Opin. Immunol. 1994;6:584–589. doi: 10.1016/0952-7915(94)90145-7. - DOI - PubMed
    1. Zasloff M. Antimicrobial peptides of multicellullar organisms. Nature. 2002;415:359–365. doi: 10.1038/415389a. - DOI - PubMed
    1. Hancock R.E.W., Sahl H.G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 2006;24:1551–1557. doi: 10.1038/nbt1267. - DOI - PubMed
    1. Lai Y., Gallo R.L. AMPed up immunity: How antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 2009;30:131–141. doi: 10.1016/j.it.2008.12.003. - DOI - PMC - PubMed

LinkOut - more resources