Retrocyclin-2: Structural analysis of a potent anti-HIV θ-defensin

Daly, Norelle L., Chen, Y, Rosengren, KJ, Marx, UC, Phillips, ML, Waring, AJ, Wang, W, Lehrer, RI and Craik, David J. (2007) Retrocyclin-2: Structural analysis of a potent anti-HIV θ-defensin. Biochemistry, 46 35: 9920-9928. doi:10.1021/bi700720e

Author Daly, Norelle L.
Chen, Y
Rosengren, KJ
Marx, UC
Phillips, ML
Waring, AJ
Wang, W
Lehrer, RI
Craik, David J.
Title Retrocyclin-2: Structural analysis of a potent anti-HIV θ-defensin
Journal name Biochemistry   Check publisher's open access policy
ISSN 0006-2960
ISBN 978-0-387-73656-3
Publication date 2007-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1021/bi700720e
Open Access Status DOI
Volume 46
Issue 35
Start page 9920
End page 9928
Total pages 9
Place of publication Washington
Publisher American Chemical Society
Language eng
Subject C1
250302 Biological and Medical Chemistry
780105 Biological sciences
Abstract Retrocyclins are circular mini-defensins with significant potential as agents against human immunodeficiency virus, influenza A, and herpes simplex virus. Retrocyclins bind carbohydrate-containing surface molecules such as gp120 and CD4 with high affinity (K-d, 10-100 nM), promoting their localization on cell membranes. The structural features important for activity have yet to be fully elucidated, but here, we have determined the first three-dimensional structure of a retrocyclin, namely, one of the most potent forms, retrocyclin-2. In the presence of SDS micelles, a well-defined beta-hairpin braced by three disulfide bonds that defines the cystine ladder motif is present. By contrast, a well-defined structure could not be determined in aqueous solution, suggesting that the presence of SDS micelles stabilizes the extended conformation of retrocyclin-2. Translational diffusion measurements indicate that retrocyclin-2 interacts with the SDS micelles, and such a membrane-like interaction may be an important feature in the mechanism of action of these antimicrobial peptides. Analytical ultracentrifugation and the NMR data indicated that retrocyclin-2 self-associates to form a trimer in a concentration-dependent manner. The ability to self-associate may contribute to the high-affinity binding of retrocyclins for glycoproteins by increasing the valency and enhancing the ability of retrocyclins to cross-link cell surface glycoproteins.
Keyword Biochemistry & Molecular Biology
Nmr Structure Calculation
Torsion Angle Dynamics
Antimicrobial Peptide
Sunflower Seeds
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID AI056921
Institutional Status UQ

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Created: Tue, 19 Feb 2008, 00:52:03 EST