Structure of an immunoglobulin Fab fragment specific for poly(dG)·poly(dC)

Clifford D. Mol, Alastair K S Muir, Jeremy S. Lee, Wayne F. Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Jel 72 is a murine monoclonal antibody that is highly specific for the right-handed DNA duplex formed by poly(dG)·poly(dC). The three-dimensional structure of the antigen-binding fragment (Fab) of Jel 72 has been determined by x-ray crystallographic methods and refined to 2.7-Å resolution. The structure has been determined using a combination of molecular replacement and multiple isomorphous replacement techniques. Crystals of Jel 72 contain two Fab fragments/asymmetric unit. The orientation of each of the four separate constant and variable domain pairs was determined from rotation function searches against appropriately oriented model Fab fragments. The rotated Fab domain pairs were placed within the unit cell using a phased translation search procedure with low resolution phases calculated from three derivatives. The two crystallographically independent Fab fragments possess 'elbow' angles (relating the variable and constant domain pairs) that differ by 14° (146° versus 132°). The shape and electrostatic surface potential of the combining site suggest a possible model for the recognition of double helical DNA. The model proposes that residues in the third hypervariable region of the heavy chain interact with the DNA bases via the major groove of poly(dG)·poly(dC). This model may be applicable to the recognition of double-stranded DNA by autoimmune antibodies that occur in systemic lupus erythematosus.

Original languageEnglish (US)
Pages (from-to)3605-3614
Number of pages10
JournalJournal of Biological Chemistry
Volume269
Issue number5
StatePublished - Feb 4 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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