FIBRINOGEN STRUCTURE IN PROJECTION AT 18-A RESOLUTION - ELECTRON-DENSITY BY COORDINATED CRYOELECTRON MICROSCOPY AND X-RAY CRYSTALLOGRAPHY

Electron microscope images of frozen-hydrated crystals of a proteolytically modified fibrinogen show excellent preservation of the structure. An electron density map of the key centric projection of the crystal at 18 Å resolution has been obtained by combining the phases derived from cryo-electron microscopy with X-ray amplitudes. Simulation methods developed in earlier studies have been used to interpret the map. In contrast to the earlier images, the map allows us to visualize the coiled-coil region of the molecule and possible substructure in the β domains. The map also shows that there is a marked difference in density in the two regions corresponding to the molecular ends where the γ domains interact. A possible interpretation of this finding is provided by assuming substructure in the γ domains and the breaking of molecular symmetry where these domains interact. Some additional constraints useful for the determination of the three-dimensional structure were obtained from cryo-electron micrographs of a perpendicular view at 25 Å resolution. Implications of this working model for the molecular length and contacts in the filaments in both the crystal and fibrin are described. The data used here will be valuable as a starting point for obtaining the three-dimensional structure. © 1991.