Abteilung Strukturforschung, Max-Planck-Institut fur Biochemie, Martinsried, Germany.
J Mol Biol 225: 739-53 (1992)
Abstract
We report the solution of the crystal structure of a mutant of the
immunoglobulin VL domain of the antibody McPC603, in which the
complementarity-determining region 1 segment is replaced with that of a
different antibody. The wild-type and mutant crystal structures have
been refined to a crystallographic R-factor of 14.9% at a nominal
resolution of 1.97 A. A detailed description of the structures is given.
Crystal packing results in a dimeric association of domains, in a
fashion closely resembling that of an Fv fragment. The comparison of
this VL domain with the same domain in the Fab fragment of McPC603 shows
that the structure of an immunoglobulin VL domain is largely
independent of its mode of association, even in places where the
inter-subunit contacts are not conserved between VL and VH. In all three
complementarity-determining regions we observe conformations that would
not have been predicted by the canonical structure hypothesis.
Significant differences between the VL domain dimer and the Fab fragment
in the third complementarity-determining region show that knowledge of
the structure of the dimerization partner and its exact mode of
association may be needed to predict the precise conformation of
antigen-binding loops.
Mesh Headings
Unique Identifier: 92292158
Chemical Identifiers (Names)