Protein-protein interaction at crystal contacts

Packing contacts are crystal artifacts, yet they make use of the same forces that govern specific recognition in protein-protein complexes and oligomeric proteins. They provide examples of a nonspecific protein-protein interaction which can be compared to biologically relevant ones, We evaluate the number and size of pairwise interfaces in 152 crystal forms where the asymmetric unit contains a monomeric protein, In those crystal forms that have no element of a-fold symmetry, we find that molecules form 8 to 10 pairwise interfaces. The total area of the surface buried on each molecule is large, up to 4400 Angstrom(2). Pairwise interfaces bury 200-1200 Angstrom(2), like interfaces generated at random in a computer simulation, and less than interfaces in protease-inhibitor or antigen-antibody complexes, which bury 1500 Angstrom(2) or more. Thus, specific contacts occurring in such complexes extend over a larger surface than nonspecific ones, In crystal forms with a-fold symmetry, pairwise interfaces are fewer and larger on average than in the absence of a-fold symmetry, Some bury 1500-2500 Angstrom(2), like interfaces in oligomeric proteins, and create ''crystal oligomers'' which may have formed in the solution before crystallizing. (C) 1995 Wiley-Liss, Inc.