title: Human defensins: synthesis and structural properties.
abstract: Defensins are small, beta-sheet-rich, cationic peptides found in many organisms. All defensins have amphiphilic properties, which are central for antimicrobial activities of the proteins. The human genome encodes many defensin-line molecules, of which 10 have been characterized. Molecules of all known human defensins are stabilized by three intramolecular disulfide bonds arranged in a conserved pattern. To date, studies of human defensins indicate that these proteins are involved in various biological processes associated primarily with defensive and regulatory responses to infections by pathological agents. A comprehensive understanding of the multiple roles played by defensins within the immune system is greatly increased by reviewing the results of detailed structural studies. Emerging structural data, derived by the X-ray crystallography and the NMR spectroscopy in solution combined with functional studies; allow a rational understanding of the different activities of defensins and the mechanisms controlling these activities. Due to their well-established antimicrobial properties, defensins are also being investigated for their potential as therapeutics agents. Recently, increased effort has been focused on studies of the immunoregulatory properties of defensins, associated with their ability to bind and activate the G(i)-protein-coupled seven-transmembrane receptors. Comprehensive studies of defensins require development of simple, efficient, and inexpensive methods to generate these proteins and their derivatives in correctly folded form. This review highlights the current status of the sample generation methods, structural studies, and the structure-function relationships for human defensins.
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Marzena
authors.initials: M
authors.lastname: Pazgier
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Li
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.forename: Jacek
authors.initials: J
authors.lastname: Lubkowski
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology; D018360:Crystallography, X-Ray; D023082:Defensins / Q000737:chemistry* / Q000145:classification / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D023082:Defensins; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins