Structural features of protein-nucleic acid recognition sites

We analyzed the atomic models of 75 X-ray structures of protein-nucleic aci d complexes with the aim of uncovering common properties. The interface are a measured the extent of contact between the protein and nucleic acid. It w as found to vary between 1120 and 5800 Angstrom(2). Despite this wide varia tion, the interfaces in complexes of transcription factors with double-stra nded DNA could be broken up into recognition modules where 12 +/- 3 nucleot ides on the DNA side contact 24 +/- 6 amino acids on the protein side, with interface areas in the range 1600 +/- 400 Angstrom(2). For enzymes acting on DNA, the recognition module is on average 600 Angstrom(2) larger, due to the requirement of making an active site. As judged by its chemical and am ino acid composition, the average protein surface in contact with the DNA i s more polar than the solvent accessible surface or the typical protein-pro tein interface. The protein side is rich in positively charged groups from lysine and arginine side chains; on the DNA side the negative charges from phosphate groups dominate. Hydrogen bonding patterns were also analyzed, an d we found one intermolecular hydrogen bond per 125 Angstrom(2) of interfac e area in high-resolution structures. An equivalent number of polar interac tions involved water molecules, which are generally abundant at protein-DNA interfaces. Calculations of Voronoi atomic volumes, performed in the prese nce and absence of water molecules, showed that protein atoms buried at the interface with DNA are on average as closely packed as in the protein inte rior. Water molecules contribute to the close packing, thereby mediating sh ape complementarity. Finally, conformational changes accompanying associati on were analyzed in 24 of the complexes for which the structure of the free protein was also available. On the DNA side the extent of deformation show ed some correlation with the size of the interface area. On the protein sid e the type and size of the structural changes spanned a wide spectrum. Diso rder-to-order transitions, domain movements, quaternary and tertiary change s were observed, and the largest changes occurred in complexes with large i nterfaces.