 |
|
Title
|
|
Novel arrangement of immunoglobulin variable domains: X-ray crystallographic analysis of the lambda-chain dimer Bence-Jones protein Loc.
|
|
|
Authors
|
|
C.H.Chang,
M.T.Short,
F.A.Westholm,
F.J.Stevens,
B.C.Wang,
W.Furey,
A.Solomon,
M.Schiffer.
|
|
|
Ref.
|
|
Biochemistry, 1985,
24,
4890-4897.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
We have characterized and crystallized a human lambda I light-chain dimer,
Bence-Jones protein Loc, which has variable (V) region antigenic determinants
characteristic for the lambda I subgroup and constant (C) region determinants of
the C lambda I gene Mcg. The crystal structure was determined to 3-A resolution;
the R factor is 0.27. The angle formed by the twofold axes of the V and C
domains, the "elbow bend", is 97 degrees, the smallest found so far for an
antibody fragment. The antigen-binding site formed by the two V domains of the
Loc light chain differs significantly from those of other immunoglobulin
molecules (light-chain dimers and Fab fragments) for which X-ray
crystallographic data are available. Whereas, in other antibody fragments, the V
domains are related by a local twofold axis, a local twofold screw axis with a
translational component of 3.5 A relates the V domains in protein Loc. In
contrast to the classic antigen binding "pocket" formed by V domain interactions
in the previously characterized antibody structures, the V region associations
in protein Loc result in a central protrusion in the binding site, with grooves
on two sides of the protrusion. The structure of protein Loc indicates that
immunoglobulins are physically capable of forming a more diverse spectrum of
antigen-binding sites than has been heretofore apparent. Moreover, the unusual
protruding nature of the binding site may be analogous to structures required
for some anti-idiotypic antibodies. Further, the complementarity-determining
residues form parts of two independent grooves.(ABSTRACT TRUNCATED AT 250 WORDS)
|
|
|
|