PROTEIN-PROTEIN CRYSTAL-PACKING CONTACTS

Protein-protein contacts in monomeric protein crystal structures have been analyzed and compared to the physiological protein-protein contac ts in oligomerization. A number of features differentiate the crystal- packing contacts from the natural contacts occurring in multimeric pro teins. The area of the protein surface patches involved in packing con tacts is generally smaller and its amino acid composition is indisting uishable from that of the protein surface accessible to the solvent. T he fraction of protein surface in crystal contacts is very variable an d independent of the number of packing contacts. The thermal motion at the crystal packing interface is intermediate between that of the sol vent-accessible surface and that of the protein core, even for large p acking interfaces, though the tendency is to be closer to that of the core. These results suggest that protein crystallization depends on ra ndom protein-protein interactions, which have little in common with ph ysiological protein-protein recognition processes, and that the possib ility of engineering macromolecular crystallization to improve crystal quality could be widened.