Journal article
The Solution Structures of the Human β-Defensins Lead to a Better Understanding of the Potent Bactericidal Activity of HBD3 against Staphylococcus aureus
The Journal of biological chemistry, Vol.277(10), pp.8279-8289
03/08/2002
DOI: 10.1074/jbc.M108830200
PMID: 11741980
Abstract
The three human β-defensins, HBD1–3, are 33–47-residue, cationic antimicrobial proteins expressed by epithelial cells. All three proteins have broad spectrum antimicrobial activity, with HBD3 consistently being the most potent. Additionally, HBD3 has significant bactericidal activity against Gram-positive Staphylococcus aureus at physiological salt concentrations. We have compared the multimeric state of the three β-defensins using NMR diffusion spectroscopy, dynamic and static light scattering, and analysis of the migration of the three β-defensins on a native gel. All three techniques are in agreement, suggesting that HBD-3 is a dimer, while HBD-1 and HBD-2 are monomeric. Subsequently, the NMR solution structures of HBD1 and HBD3 were determined using standard homonuclear techniques and compared with the previously determined solution structure of HBD2. Both HBD1 and HBD3 form well defined structures with backbone root mean square deviations of 0.451 and 0.616 Å, respectively. The tertiary structures of all three β-defensins are similar, with a short helical segment preceding a three-stranded antiparallel β-sheet. The surface charge density of each of the defensins is markedly different, with the surface of HBD3 significantly more basic. Analysis of the NMR data and structures led us to suggest that HBD3 forms a symmetrical dimer through strand β2 of the β-sheet. The increased anti-Staphylococcalactivity of HBD3 may be explained by the capacity of the protein to form dimers in solution at low concentrations, an amphipathic dimer structure, and the increased positive surface charge compared with HBD1 and HBD2.
Details
- Title: Subtitle
- The Solution Structures of the Human β-Defensins Lead to a Better Understanding of the Potent Bactericidal Activity of HBD3 against Staphylococcus aureus
- Creators
- David J Schibli - Structural Biology Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, CanadaHoward N Hunter - Structural Biology Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, CanadaVladimir Aseyev - Department of Chemical and Biochemical Engineering, University of Iowa, Iowa City, Iowa 52242Timothy D Starner - Departments of Pediatrics, Iowa City, Iowa 52242John M Wiencek - Department of Chemical and Biochemical Engineering, University of Iowa, Iowa City, Iowa 52242Paul B McCray - Departments of Pediatrics, Iowa City, Iowa 52242Brian F Tack - §Microbiology, University of Iowa College of Medicine, Iowa City, Iowa 52242Hans J Vogel - Structural Biology Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.277(10), pp.8279-8289
- DOI
- 10.1074/jbc.M108830200
- PMID
- 11741980
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 03/08/2002
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093226502771
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