 |
|
Title
|
|
Small rearrangements in structures of Fv and Fab fragments of antibody D1.3 on antigen binding.
|
|
|
Authors
|
|
T.N.Bhat,
G.A.Bentley,
T.O.Fischmann,
G.Boulot,
R.J.Poljak.
|
|
|
Ref.
|
|
Nature, 1990,
347,
483-485.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The potential use of monoclonal antibodies in immunological, chemical and
clinical applications has stimulated the protein engineering and expression of
Fv fragments, which are heterodimers consisting of the light and heavy chain
variable domains (VL and VH) of antibodies. Although Fv fragments exhibit
antigen binding specificity and association constants similar to their parent
antibodies or Fab moieties, similarity in their interactions with antigen at the
level of three-dimensional structure has not been investigated. We have
determined the high-resolution crystal structure of the genetically engineered
FvD1.3 fragment of the anti-hen egg-white lysozyme (HEL) monoclonal antibody
D1.3, and of its complex with HEL. On comparison with the crystallographically
refined FabD1.3-HEL complex, we find that FvD1.3 and FabD1.3 make, with minor
exceptions, very similar contacts with the antigen. Furthermore, a small but
systematic rearrangement of the domains of FvD1.3 occurs on binding HEL,
bringing the contacting residues closer to the antigen by a mean value of about
0.7 A for VH (aligning on VL) or of 0.5 A for VL (aligning on VH). This is
indicative of an induced fit rather than a 'lock and key' fit to the antigen.
|
|
|
|