2. Academic Validation
  3. Rattusin structure reveals a novel defensin scaffold formed by intermolecular disulfide exchanges

Rattusin structure reveals a novel defensin scaffold formed by intermolecular disulfide exchanges

  • Sci Rep. 2017 Mar 27:7:45282. doi: 10.1038/srep45282.
Hye Jung Min 1 2,  Hyosuk Yun 1,  Sehyeon Ji 1,  Ganesan Rajasekaran 3,  Jae Il Kim 4,  Jeong-Sun Kim 1,  Song Yub Shin 3,  Chul Won Lee 1
Affiliations

Affiliations

  • 1 Department of Chemistry, Chonnam National University, Gwangju 61186, South Korea.
  • 2 Department of Pharmaceutical Cosmetics, Kwangju Women's University, Gwangju 62396, South Korea.
  • 3 Department of Medical Science, Graduate School and Department of Cellular and Molecular Medicine, School of Medicine, Chosun University, Gwangju 61452, South Korea.
  • 4 Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 61005, South Korea.
PMID: 28345637 DOI: 10.1038/srep45282
Abstract

Defensin peptides are essential for innate immunity in humans and Other living systems, as they provide protection against infectious pathogens and regulate the immune response. Here, we report the solution structure of rattusin (RTSN), an α-defensin-related peptide, which revealed a novel C2-symmetric disulfide-linked dimeric structure. RTSN was synthesized by solid-phase peptide synthesis (SPPS) and refolded by air oxidation in vitro. Dimerization of the refolded RTSN (r-RTSN) resulted from five intermolecular disulfide (SS) bond exchanges formed by ten cysteines within two protomer chains. The SS bond pairings of r-RTSN were determined by mass analysis of peptide fragments cleaved by trypsin digestion. In addition to mass analysis, nuclear magnetic resonance (NMR) experiments for a C15S mutant and r-RTSN confirmed that the intermolecular SS bond structure of r-RTSN showed an I-V', II-IV', III-III', IV-II', V-I' arrangement. The overall structure of r-RTSN exhibited a cylindrical array, similar to that of β-sandwich folds, with a highly basic surface. Furthermore, fluorescence spectroscopy results suggest that r-RTSN exerts bactericidal activity by damaging membrane integrity. Collectively, these results provide a novel structural scaffold for designing highly potent peptide-based Antibiotics suitable for use under various physiological conditions.

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