title: Protein motion and lock and key complementarity in antigen-antibody reactions.
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 (10(7)-10(11) M-1). By contrast, in an idiotope--anti-idiotope (antibody-antibody) reaction, which is entropically driven, the binding equilibrium constant is only 1.5 x 10(5) M-1 at 20 degrees C. This low value results from a slow association rate (10(3) 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 x 10(8) 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 x 10(5) 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.
authors.affiliation: CARB, University of Maryland Biotechnology Institute, Rockville 20850, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Braden
authors.forename: W
authors.initials: W
authors.lastname: Dall'Acqua
authors.forename: E
authors.initials: E
authors.lastname: Eisenstein
authors.forename: B A
authors.initials: BA
authors.lastname: Fields
authors.forename: F A
authors.initials: FA
authors.lastname: Goldbaum
authors.forename: E L
authors.initials: EL
authors.lastname: Malchiodi
authors.forename: R A
authors.initials: RA
authors.lastname: Mariuzza
authors.forename: F P
authors.initials: FP
authors.lastname: Schwarz
authors.forename: X
authors.initials: X
authors.lastname: Ysern
authors.forename: R J
authors.initials: RJ
authors.lastname: Poljak
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions / Q000502:physiology*; D006801:Humans; D007135:Immunoglobulin Variable Region; D011506:Proteins / Q000737:chemistry*
chemical_list: D007135:Immunoglobulin Variable Region; D011506:Proteins