Conformational preferences of synthetic peptides derived from the immunodominant site of the circumsporozoite protein of Plasmodium falciparum by 1H NMR

Biochemistry. 1990 Aug 28;29(34):7828-37. doi: 10.1021/bi00486a008.

Abstract

Proton nuclear magnetic resonance and ultraviolet circular dichroism spectroscopy have been used to probe the conformational ensemble of the tandemly repeating tetrapeptide unit of the circumsporozoite coat protein of the malaria parasite Plasmodium falciparum. Peptides based on the Asn-Ala-Asn-Pro and Asn-Pro-Asn-Ala cadences and composed of one to three tetrapeptide units were synthesized and examined using one- and two-dimensional NMR spectroscopy. The chemical shift of the amide protons, the temperature dependence of the amide proton chemical shift, and the patterns of NOE connectivities in the various peptides give evidence for the presence of a substantial population of folded conformers in several of the peptides in water solution at pH 5.0. Correlations between the behavior of the tandemly repeated units in different peptides have been used to infer the structure(s) of the folded conformers. The data are consistent with the presence of turnlike structures stabilized by hydrogen bonding of the backbone amide protons of the alanines and the asparagine residues preceding them. Specific differences in the strengths of NOEs between peptides of different lengths indicate that the folded structure is considerably stabilized by the presence of the asparagine residue following the alanine. Differences between peptides with different cadences of the tandemly repeating unit indicate that a repeating structural motif is formed by the Asn-Pro-Asn-Ala-(Asn) cadence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / chemistry*
  • Antigens, Protozoan / immunology
  • Binding Sites
  • Circular Dichroism
  • Hydrogen
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Plasmodium falciparum / immunology*
  • Protein Conformation
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / immunology
  • Protozoan Vaccines / chemistry*
  • Structure-Activity Relationship
  • Temperature

Substances

  • Antigens, Protozoan
  • Protozoan Proteins
  • Protozoan Vaccines
  • circumsporozoite protein, Protozoan
  • Hydrogen