Conformational Selection and Induced Fit in Specific Antibody and Antigen Recognition: SPE7 as a Case Study
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Abstract
Antibody-antigen specific recognition is essential in autoimmunity. In this study, antibody SPE7 binding to protein antigens and to hapten molecules were carefully analyzed in order to gain insight into their binding mechanisms. X-ray crystal structures show that SPE7 can adopt at least four different conformations, as in the two observed free isomers (Ab(1) and Ab(2)) and the two observed bound conformers (Ab(3) and Ab(4)). Multidimensional scaling analysis reveals that antibody SPE7 may obey a global conformational selection mechanism upon its binding to an antigen. The conformations of key residue at the binding site (Trp93L) further reveals that bound isomer Ab(3) may come from free isomer Ab(2), and bound isomer Ab(4) from free isomer Ab(1). The average root-mean-square deviation (RMSD) values between the bound isomers and the corresponding free isomers and Kolmogorov-Smimov P test analysis indicate that the antibody may also follow a local induced fit mechanism at the binding interface. Quantitative analysis indicates that the magnitude of the local induced fit interaction at the binding site is more pronounced than that of the global conformational selection interaction. These conclusions are further supported by high-temperature unbinding kinetics analysis. The computational methods proposed here can also be used to study the specific recognitions between other antibody and antigen systems.