V(L):V(H) domain rotations in engineered antibodies: Crystal structures of the fab fragments from two murine antitumor antibodies and their engineered human constructs

M. J. Banfield, D. J. King, A. Mountain, R. L. Brady*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

46 Citations (Scopus)

Abstract

The crystal structures of two pairs of Fab fragments have been determined. The pairs comprise both a murine and an engineered human form, each derived from the antitumor antibodies A5B7 and CTM01. Although antigen specificity is maintained within the pairs, antigen affinity varies. A comparison of the hypervariable loops for each pair of antibodies shows their structure has been well maintained in grafting, supporting the canonical loop model. Detailed structural analysis of the binding sites and domain arrangements for these antibodies suggests the differences in antigen affinity observed are likely to be due to inherent flexibility of the hypervariable loops and movements at the V(L):V(H) domain interface. The four structures provide the first opportunity to study in detail the effects of protein engineering on specific antibodies.

Original languageEnglish
Pages (from-to)161-171
Number of pages11
JournalProteins: Structure, Function and Genetics
Volume29
Issue number2
DOIs
Publication statusPublished - 1 Jan 1997

Keywords

  • Antibody humanization
  • Complementarity- determining region
  • Protein
  • Quaternary structure

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