Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Significant structural and functional change of an antigen-binding site by a distant amino-acid substitution - proposal of a structural mechanism

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Chien, N. C.
  • Roberts, V. A.
  • Giusti, A. M.
  • Scharff, M. D.
  • Getzoff, Elizabeth

publication date

  • July 1989

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • To study the molecular basis for antibody diversity and the structural basis for antigen binding, we have characterized the loss of phosphocholine (P-Cho) binding both experimentally and computationally in U10, a somatic mutant of the antibody S107. Nucleotide sequencing of U10 shows a single base change in JH1, substituting Asp-101 with Ala, over 9 A distant from the P-Cho-binding pocket. Probing with antiidiotypic antibodies suggests local, not global, conformational changes. Computational results support a specific structural mechanism for the loss of P-Cho binding. The U10 mutation eliminates the charged interaction between Asp-101 and Arg-94, which allows the Arg-94 side chain to disrupt P-Cho binding sterically and electrostatically by folding into the P-Cho-binding site. These results specifically show the importance of the Arg-94 to Asp-101 side chain salt bridge in the heavy-chain CDR3 conformation and suggest that residues distant from the binding site play an important role in antibody diversity and inducible complementarity.

subject areas

  • Animals
  • Antibodies
  • Antibody Diversity
  • Antigen-Antibody Complex
  • Antigens
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Computer Simulation
  • Enzyme-Linked Immunosorbent Assay
  • Gene Rearrangement
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Phosphorylcholine
  • Protein Conformation
  • Structure-Activity Relationship
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.86.14.5532

PubMed ID

  • 2748602
scroll to property group menus

Additional Document Info

start page

  • 5532

end page

  • 5536

volume

  • 86

issue

  • 14

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support