1ma4
Solution Structure of Tachyplesin I Mutant TPY4 in water
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OverviewOverview
Tachyplesin I is a 17-residue peptide isolated from the horseshoe crab, Tachypleus tridentatus.It has high antimicrobial activity and adopts a, beta-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 beta-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 beta-hairpin is, stabilized by aromatic ring stacking interactions. This is supported by, experiments in which the beta-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 beta-hairpin, fold in solution and the ability to rearrange critical side chain residues, upon membrane association.
About this StructureAbout this Structure
1MA4 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Solution and micelle-bound structures of tachyplesin I and its active aromatic linear derivatives., Laederach A, Andreotti AH, Fulton DB, Biochemistry. 2002 Oct 15;41(41):12359-68. PMID:12369825
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