UC Irvine

Using the refined molecular structure of the Gene 5 DNA Binding Protein (G5BP) and the mechanism of DNA binding deduced from a variety of experimental techniques (G. D. Brayer and A. McPherson, J. Mol. Biol. 169, 565, 1983; G. D. Brayer and A. McPherson, Biochemistry 23, 340, 1984), we have modeled the contiguous, linear aggregation of G5BP dimers along two opposing single strands of DNA. Using both automated graphics systems and systematic calculations of intermolecular contacts between adjacent units, we have optimized the fit of complementary protein surfaces in the presence of DNA. We propose that a minor conformational change involving residues 38-43, triggered by the binding of nucleic acid, relieves several critical steric contacts and permits otherwise extensively complementary surfaces to form an interface. The bonding between surfaces on adjacent G5BP units is the primary source of the cooperativity of binding observed for G5BP. The interacting amino acid residues at the interface are described.