Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 A

Science. 1990 May 11;248(4956):712-9. doi: 10.1126/science.2333521.

Abstract

The three-dimensional structures of an antibody to a peptide and its complex with the peptide antigen have been determined at 2.8 A resolution. The antigen is a synthetic 19-amino acid peptide homolog of the C helix of myohemerythrin (Mhr). The unliganded Fab' crystals are orthorhombic with two molecules per asymmetric unit, whereas the complex crystals are hexagonal with one molecule per asymmetric unit. The Fab' and the Fab'-peptide complex structures have been solved independently by molecular replacement methods and have crystallographic R factors of 0.197 and 0.215, respectively, with no water molecules included. The amino-terminal portion of the peptide sequence (NH2-Glu-Val-Val-Pro-His-Lys-Lys) is clearly interpretable in the electron density map of the Fab'-peptide complex and adopts a well-defined type II beta-turn in the concave antigen binding pocket. This same peptide amino acid sequence in native Mhr is alpha-helical. The peptide conformation when bound to the Fab' is inconsistent with binding of the Fab' to native Mhr, and suggests that binding of the Fab' to conformationally altered forms of the native Mhr or to apo-Mhr. Immunological mapping previously identified this sequence as the peptide epitope, and its fine specificity correlates well with the structural analysis. The binding pocket includes a large percentage of hydrophobic residues. The buried surfaces of the peptide and the antibody are complementary in shape and cover 460 A2 and 540 A2, respectively. These two structures now enable a comparison of a specific monoclonal Fab' both in its free and antigen complexed state. While no major changes in the antibody were observed when peptide was bound, there were some small but significant side chain and main chain rearrangements.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antigen-Antibody Complex*
  • Crystallization
  • Hemerythrin* / analogs & derivatives
  • Hemerythrin* / immunology
  • Immunoglobulin Fab Fragments*
  • Metalloproteins* / immunology
  • Models, Molecular*
  • Molecular Sequence Data
  • Peptides / immunology*
  • Pigments, Biological
  • Protein Conformation
  • Software
  • X-Ray Diffraction

Substances

  • Antigen-Antibody Complex
  • Hemerythrin
  • Immunoglobulin Fab Fragments
  • Metalloproteins
  • Peptides
  • Pigments, Biological
  • myohemerythrin