The Precise and Entire Antigenic Structure of Lysozyme: Implications of Surface-Simulation Synthesis and the Molecular Features of Protein Antigenic Sites

Summary

Intensive research in the author’s laboratory over a 10-year period has now culminated in the precise determination of the entire antigenic structure of native hen egg-white lysozyme. The protein carries three antigenic sites. Each site is made up of spatially adjacent surface residues that are not in direct peptide linkage. The residues of each site describe an imaginary line which circumscribes part of the surface topography of the protein and act functionally towards the antibody as if they are in direct peptide bond linkage. The reactivity of each site is fully satisfied by an appropriate surface-simulation synthetic peptide, and the three synthetic sites account for the full immunochemical reactivity of the native protein. Each site is subject to conformational restrictions and exhibits directionality which is a function of side chain orientations. The antigenic sites of myoglobin and lysozyme are compared. It is proposed that antigenic sites of the type found in myoglobin are called “continuous sites”, while antigenic sites of the type seen in lysozyme are defined as “discontinuous sites”.

The unorthodox and novel concept of “surface-simulation” synthesis, which we developed for the precise definition of the antigenic sites of lysozyme, links the spatially adjacent residues constituting a site directly via peptide bonds with appropriate spacers where necessary. Application of this concept has enabled us to mimick synthetically, at least in terms of binding function, the antibody combining sites to lysozyme antigenic sites. The implications and potential applications of surface-simulation synthesis are discussed.