Structural features of the reactions between antibodies and protein antigens.
Antibodies bind protein antigens over large sterically and electrostatically complementary surfaces. Van der Waals forces, hydrogen bonds, and occasionally ion pairs provide stability to antibody-antigen complexes. In addition, water molecules contribute hydrogen bonds linking antigen and antibody, and increase the complementarity of antigen-antibody interfaces. In qualification to a strict 'lock and key' mechanism, evidence of conformational changes between free and complexed antibodies indicate some accommodation to the antigen. Antibody-protein antigen reactions are enthalpically driven with varying degrees of entropic compensation, often dependent on the magnitude of the enthalpy of the reaction. In the case of two antibody-combining sites studied by X-ray diffraction, the relative arrangements of the variable domains of the light and heavy chains of the antibody change slightly from the free to the antigen-bound state. Furthermore, the contacting residues of both antibodies exhibit similar reduced mobilities when complexed to antigen, suggesting that differences in 'solvent entropy' rather than in conformational freedom may be the source of different entropic compensation factors. In concert, data from structural studies, reaction rates, calorimetric measurements, molecular dynamics simulations, and site-directed mutagenesis are beginning to detail the nature of antibody-protein antigen interactions.
Braden
B C
BC
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850.
Poljak
R J
RJ
D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism; D000918:Antibody Specificity; D000941:Antigens / Q000737:chemistry* / Q000378:metabolism; D001666:Binding Sites, Antibody; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007700:Kinetics; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry / Q000276:immunology*; D013816:Thermodynamics
D000906:Antibodies; D000941:Antigens; D011506:Proteins