1MA4

Solution Structure of Tachyplesin I Mutant TPY4 in water

Summary for 1MA4

• Entry DOI: 10.2210/pdb1ma4/pdb
• Related: 1MA2 1MA5 1MA6
• NMR Information: BMRB: 5486,5487,5488,5489
• Descriptor: Tachyplesin 1 (1 entity in total)
• Functional Keywords: tachyplesin i, beta hairpin, tyrosine mutant, tpy4, antimicrobial protein
• Cellular location: Secreted: P14213
• Total number of polymer chains: 1
• Total formula weight: 2514.93

Authors

Laederach, A.,Andreotti, A.H.,Fulton, D.B. (deposition date: 2002-07-31, release date: 2002-10-16, Last modification date: 2024-05-22)

Primary citation

Laederach, A.,Andreotti, A.H.,Fulton, D.B.
Solution and micelle-bound structures of Tachyplesin I and its active linear derivatives
Biochemistry, 41:12359-12368, 2002

PubMed Abstract: 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.

PubMed: 12369825
DOI: 10.1021/bi026185z

Experimental method

SOLUTION NMR