Antibody flexibility observed in antigen binding and its subsequent signaling

Antibodies are well-known proteins that defend against bacterial and viral infections. At the molecular level, antibodies in solution are flexible and exist in populations of different structures with different energy levels which are important for antigen binding and immunological functions. In the present post-genome era, although many three-dimensional structures of proteins, including antibodies, have been determined mainly by X-ray structural analysis, quantitative analyses of the dynamic properties of proteins are needed for correlation with the protein functions. Since protein molecules always function via binding, we have investigated the binding mechanism of antibodies and the conformational change of antibodies induced upon antigen binding, which is critical for intracellular signaling. In this article, I review several reports, including our recent results of dynamic structural analyses for antibodies. These reports strongly suggest the difficulty in interpreting snapshot pictures from static structural analyses. To detect the flexible nature of protein, the development or improvement of several techniques is also in progress. Used together, the conventional methods, such as binding thermodynamics and kinetics, can provide new information on protein flexibility. These novel findings can not only shed light on the general features of protein functions but also can be put to practical use, such as the rational design of an antibody with high antigen-binding affinity.