PROTEIN CRYSTALLIZATION

Crystallization is necessary to obtain the three-dimensional structure of proteins and nucleic acids; it often represents the bottleneck in structure determination. Our understanding of crystallization mechanis ms is still incomplete. In this review, we emphasize fundamental aspec ts of the crystallization process. Protein-protein contacts in crystal s are complex, involving a delicate balance of specific and nonspecifi c interactions. Depending on solution conditions, these interactions c an lead to nucleation of crystals or to amorphous aggregation; this st age of crystallization has been successfully studied by light scatteri ng. Postnucleation crystal growth may proceed by mechanisms involving crystal defects or two-dimensional nucleation, as observed by atomic f orce and interference microscopy. Cessation of growth has been observe d but remains incompletely understood. Impurities may play important r oles during all stages of crystallization. Phase diagrams can guide op timization of conditions for nucleation and subsequent crystal growth; a theoretical understanding relating these to the intermolecular inte ractions is beginning to develop.