Functional Molecular Anatomy of Fibrinogen: Antibodies as Biological Probes of Structure

Abstract

Among the more basic and exciting issues in molecular biology is the elucidation of functional molecular anatomy—the relationship between the molecular structure at all levels and the manifest functions of the molecule. Significant advances in elucidation of general protein structure at all levels of organization have been realized in the past two decades, to a great extent as the result of new and incisive analytical approaches. Major contributions by physicochemical and biochemical methods have provided probes of conformation as well as the primary structure of proteins. Conformational analysis has proven most difficult, and early information was to a great extent inferential and derived from hydrodynamic data. Multidisciplinary approaches including X-ray diffraction, high-resolution ultrastructural visualization, light scattering, optical rotatory dispersion, and functional reconstruction have amassed data from which molecular conformation can frequently be deduced. Among the analytical approaches have been those in which the immune response and the products of that response are analyzed and employed as analytical probes of the basic structure and conformation of a subject molecule. Although the major emphasis in molecular immunology and immunochemistry has been the characterization of the immune response, applied immunochemistry has in no little part contributed to our understanding of molecular structure at all levels of organization (Dorrington and Tanford, 1970; Anfinsen, 1959; Kendrew et al., 1960; Scheraga, 1961; Muirhead and Perutz, 1963).