Open AccessThree-dimensional solution structure of the complex of α-bungarotoxin with a library-derived peptide
Author(s) -
Tali Scherf,
Moshe Balass,
Sara Fuchs,
Ephraim KatchalskiKatzir,
Jacob Anglister
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.12.6059
Subject(s) - peptide , chemistry , stereochemistry , residue (chemistry) , peptide library , bungarotoxin , protein structure , nuclear magnetic resonance spectroscopy , binding site , peptide sequence , acetylcholine receptor , receptor , biochemistry , gene
The solution structure of the complex between α-bungarotoxin (α-BTX) and a 13-residue library-derived peptide (MRYYESSLKSYPD) has been solved using two-dimensional proton–NMR spectroscopy. The bound peptide adopts an almost-globular conformation resulting from three turns that surround a hydrophobic core formed by Tyr-11 of the peptide. The peptide fills an α-BTX pocket made of residues located at fingers I and II, as well as at the C-terminal region. Of the peptide residues, the largest contact area is formed by Tyr-3 and Tyr-4. These findings are in accord with the previous data in which it had been shown that substitution of these aromatic residues by aliphatic amino acids leads to loss of binding of the modified peptide with α-BTX. Glu-5 and Leu-8, which also remarkably contribute to the contact area with the toxin, are present in all the library-derived peptides that bind strongly to α-BTX. The structure of the complex may explain the fact that the library-derived peptide binds α-BTX with a 15-fold higher affinity than that shown by the acetylcholine receptor peptide (α185–196). Although both peptides bind to similar sites on α-BTX, the latter adopts an extended conformation when bound to the toxin [Basus, V., Song, G. & Hawrot, E. (1993)Biochemistry 32, 12290–12298], whereas the library peptide is nearly globular and occupies a larger surface area of α-BTX binding site.