Protein motion and lock and key complementarity in antigen-antibody reactions

doi:10.1016/0031-6865(94)00046-X

Pharmaceutica Acta Helvetiae

Volume 69, Issue 4, March 1995, Pages 225-230

Pharmaceutica Acta H...

https://doi.org/10.1016/0031-6865(94)00046-X Get rights and content

Abstract

Antibodies possess a highly complementary combining site structure to that of their specific antigens. In many instances their reactions are driven by enthalpic factors including, at least in the case of the reaction of monoclonal antibody D1.3 with lysozyme, enthalpy of solvation. They require minor structural rearrangements, and their equilibrium association constants are relatively high (10⁷–10¹¹ M⁻¹). By contrast, in an idiotope-anti-idiotope (antibody-antibody) reaction, which is entropically driven, the binding equilibrium constant is only 1.5 × 10⁵ M⁻¹ at 20 °C. This low value results from a slow association rate (10³ M⁻¹ s⁻¹) due to a selection of conformational states that allow one of the interacting molecular surfaces (the idiotope on antibody D1.3) to become complementary to that of the anti-idiotopic antibody. Thus, antibody D1.3 reacts with two different macromolecules: with its specific antigen, hen egg lysozyme, and with a specific anti-idiotopic antibody. Complementarity with lysozyme is closer to a “lock and key” model and results in high affinity (2−4 × 10⁸ M⁻¹). That with the anti-idiotopic antibody involves conformational changes at its combining site and it results in a lower association constant (1.5 × 10⁵ M⁻¹). Thus, an “induced fit” mechanism may lead to a broadening of the binding specificity but with a resulting decrease in the intrinsic binding affinity which may weaken the physiological function of antibodies.

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Regular paperProtein motion and lock and key complementarity in antigen-antibody reactions

Abstract

J. Mol. Biol.

J. Biol. Chem.

Mol. Immunol.

J. Immunol. Meth.

Curr. Opinion Immunol.

Mol. Immunol.

The three-dimensional structure of an antigen-antibody complex at 2.8 Å resolution

Science

Three-dimensional structure of an idiotope-anti-idiotope complex

Nature

Small rearrangements in structures of Fv and Fab fragments of antibody D1.3 on antigen binding

Nature

Bound water molecules and conformational stabilization help mediate an antigen—antibody association

Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex

Regular paper
Protein motion and lock and key complementarity in antigen-antibody reactions