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Article
Solution and Micelle-Bound Structures of Tachyplesin I and Its Active Aromatic Linear Derivatives
Biochemistry
  • Alain Laederach, Iowa State University
  • Amy H. Andreotti, Iowa State University
  • D. Bruce Fulton, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
9-1-2002
DOI
10.1021/bi026185z
Abstract
Tachyplesin I is a 17-residue peptide isolated from the horseshoe crab, Tachyplesus tridentatus. It has high antimicrobial activity and adopts a β-hairpin conformation in solution stabilized by two cross-strand disulfide bonds. We report an NMR structural investigation of wild-type tachyplesin I and three linear derivatives (denoted TPY4, TPF4, and TPA4 in which the bridging cysteine residues are uniformly replaced with tyrosine, phenylalanine, and alanine, respectively). The three-dimensional aqueous solution structures of the wild type and the active variant TPY4 reveal very similar β-hairpin conformations. In contrast, the inactive variant TPA4 is unstructured in solution. The arrangement of the tyrosine side chains in the TPY4 structure suggests that the β-hairpin is stabilized by aromatic ring stacking interactions. This is supported by experiments in which the β-hairpin structure of TPF4 is disrupted by the addition of phenol, but not by the addition of an equimolar amount of cyclohexanol. We have also determined the structures of wild-type tachyplesin I and TPY4 in the presence of dodecylphosphocholine micelles. Both peptides undergo significant conformational rearrangement upon micelle association. Analysis of the micelle-associated peptide structures shows an increased level of exposure of specific hydrophobic side chains and an increased hydrophobic integy moment. Comparison of the structures in micelle and aqueous solution for both wild-type tachyplesin I and TPY4 reveals two requirements for high antimicrobial activity:  a β-hairpin fold in solution and the ability to rearrange critical side chain residues upon membrane association.
Comments

Reprinted (adapted) with permission from Biochemistry 41 (2002): 12359, doi:10.1021/bi026185z. Copyright 2014 American Chemical Society.

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Copyright Owner
American Chemical Society
Language
en
File Format
application/pdf
Citation Information
Alain Laederach, Amy H. Andreotti and D. Bruce Fulton. "Solution and Micelle-Bound Structures of Tachyplesin I and Its Active Aromatic Linear Derivatives" Biochemistry Vol. 41 Iss. 41 (2002) p. 12359 - 12368
Available at: http://works.bepress.com/amy_andreotti/1/