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Science 22 March 1991:
Vol. 251. no. 5000, pp. 1481 - 1485
DOI: 10.1126/science.2006422
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Articles

Science, Vol 251, Issue 5000, 1481-1485
Copyright © 1991 by American Association for the Advancement of Science

articles

Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization

CP Hill, J Yee, ME Selsted, and D Eisenberg

Eisenberg, Molecular Biology Institute, Los Angeles, CA.

Defensins (molecular weight 3500 to 4000) act in the mammalian immune response by permeabilizing the plasma membranes of a broad spectrum of target organisms, including bacteria, fungi, and enveloped viruses. The high-resolution crystal structure of defensin HNP-3 (1.9 angstrom resolution, R factor 0.19) reveals a dimeric beta sheet that has an architecture very different from other lytic peptides. The dimeric assembly suggests mechanisms by which defensins might bind to and permeabilize the lipid bilayer.


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Released ATP Is an Extracellular Cytotoxic Mediator in Salivary Histatin 5-Induced Killing of Candida albicans.
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Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents.
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Engineered Salt-insensitive alpha -Defensins with End-to-end Circularized Structures.
Q. Yu, R. I. Lehrer, and J. P. Tam (2000)
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G. Zhang, H. Hiraiwa, H. Yasue, H. Wu, C. R. Ross, D. Troyer, and F. Blecha (1999)
J. Biol. Chem. 274, 24031-24037
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Structure-Function Analysis of Tritrypticin, an Antibacterial Peptide of Innate Immune Origin.
S. Nagpal, V. Gupta, K. J. Kaur, and D. M. Salunke (1999)
J. Biol. Chem. 274, 23296-23304
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Lentivirus-derived antimicrobial peptides: increased potency by sequence engineering and dimerization.
S. B. Tencza, D. J. Creighton, T. Yuan, H. J. Vogel, R. C. Montelaro, and T. A. Mietzner (1999)
J. Antimicrob. Chemother. 44, 33-41
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Antimicrobial defensin peptides of the human ocular surface.
R. J. Haynes, P. J. Tighe, and H. S. Dua (1999)
Br. J. Ophthalmol. 83, 737-741
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Interaction of the Cyclic Antimicrobial Cationic Peptide Bactenecin with the Outer and Cytoplasmic Membrane.
M. Wu and R. E. W. Hancock (1999)
J. Biol. Chem. 274, 29-35
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Critical Role of Lipid Composition in Membrane Permeabilization by Rabbit Neutrophil Defensins.
K. Hristova, M. E. Selsted, and S. H. White (1997)
J. Biol. Chem. 272, 24224-24233
   Abstract »    Full Text »    PDF »
Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3.
W. I. Lencer, G. Cheung, G. R. Strohmeier, M. G. Currie, A. J. Ouellette, M. E. Selsted, and J. L. Madara (1997)
PNAS 94, 8585-8589
   Abstract »    Full Text »    PDF »
Epithelial antibiotic induced in states of disease.
E. D. Stolzenberg, G. M. Anderson, M. R. Ackermann, R. H. Whitlock, and M. Zasloff (1997)
PNAS 94, 8686-8690
   Abstract »    Full Text »    PDF »
Sensitivity of Periodontal Pathogens to the Bactericidal Activity of Synthetic Protegrins, Antibiotic Peptides Derived from Porcine Leukocytes.
K.T. Miyasaki, R. Iofel, and R.I. Lehrer (1997)
Journal of Dental Research 76, 1453-1459
   Abstract »    PDF »
Defensin Stimulates the Binding of Lipoprotein (a) to Human Vascular Endothelial and Smooth Muscle Cells.
A. A.-R. Higazi, E. Lavi, K. Bdeir, A. M. Ulrich, D. G. Jamieson, D. J. Rader, D. C. Usher, W. Kane, T. Ganz, and D. B. Cines (1997)
Blood 89, 4290-4298
   Abstract »    Full Text »    PDF »
Mode of Action of the Antimicrobial Peptide Indolicidin.
T. J. Falla, D. N. Karunaratne, and R. E.W. Hancock (1996)
J. Biol. Chem. 271, 19298-19303
   Abstract »    Full Text »    PDF »
Defensin Modulates Tissue-type Plasminogen Activator and Plasminogen Binding to Fibrin and Endothelial Cells.
A. A.-R. Higazi, T. Ganz, K. Kariko, and D. B. Cines (1996)
J. Biol. Chem. 271, 17650-17655
   Abstract »    Full Text »    PDF »
Fungal Membrane Responses Induced by Plant Defensins and Thionins.
K. Thevissen, A. Ghazi, G. W. De Samblanx, C. Brownlee, R. W. Osborn, and W. F. Broekaert (1996)
J. Biol. Chem. 271, 15018-15025
   Abstract »    Full Text »    PDF »
The Isolation and Characterization of a Novel Corticostatin/Defensin-like Peptide from the Kidney.
A. Bateman, R. J. MacLeod, P. Lembessis, J. Hu, F. Esch, and S. Solomon (1996)
J. Biol. Chem. 271, 10654-10659
   Abstract »    Full Text »    PDF »
NK-lysin, a Disulfide-containing Effector Peptide of T-lymphocytes, Is Reduced and Inactivated by Human Thioredoxin Reductase.
M. Andersson, A. Holmgren, and G. Spyrou (1996)
J. Biol. Chem. 271, 10116-10120
   Abstract »    Full Text »    PDF »
Role of the Leader and Structural Regions of Prelantibiotic Peptides as Assessed by Expressing Nisin-Subtilin Chimeras in Bacillus subtilis 168, and Characterization of their Physical, Chemical, and Antimicrobial Properties.
A. Chakicherla and J. N. Hansen (1995)
J. Biol. Chem. 270, 23533-23539
   Abstract »    Full Text »    PDF »
Ubiquitous natural antibiotics.
J. Gabay (1994)
Science 264, 373-374
   PDF »
The crystal structure of lysin, a fertilization protein.
A Shaw, D. McRee, V. Vacquier, and C. Stout (1993)
Science 262, 1864-1867
   Abstract »    PDF »
Characterization of Luminal Paneth Cell alpha -Defensins in Mouse Small Intestine. ATTENUATED ANTIMICROBIAL ACTIVITIES OF PEPTIDES WITH TRUNCATED AMINO TERMINI.
A. J. Ouellette, D. P. Satchell, M. M. Hsieh, S. J. Hagen, and M. E. Selsted (2000)
J. Biol. Chem. 275, 33969-33973
   Abstract »    Full Text »    PDF »
The Structure of Human beta -Defensin-2 Shows Evidence of Higher Order Oligomerization.
D. M. Hoover, K. R. Rajashankar, R. Blumenthal, A. Puri, J. J. Oppenheim, O. Chertov, and J. Lubkowski (2000)
J. Biol. Chem. 275, 32911-32918
   Abstract »    Full Text »    PDF »
Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells.
G. Yue, D. Merlin, M. E. Selsted, W. I. Lencer, J. L. Madara, and D. C. Eaton (2002)
Am J Physiol Gastrointest Liver Physiol 282, G757-G765
   Abstract »    Full Text »    PDF »


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