Structural studies of protein–nucleic acid interaction: the sources of sequence-specific binding

Abstract

Structural studies of DNA-binding proteins and their complexes with DNA have proceeded at an accelerating pace in recent years due to important technical advances in molecular genetics, DNA synthesis, protein crystallography and nuclear magnetic resonance. The last major review on this subject by Pabo & Sauer (1984) summarized the structural and functional studies of the three sequence-specific DNA-binding proteins whose crystal structures were then known, theE. colicatabolite gene activator protein (CAP) (McKay & Steitz, 1981; McKayet al.1982; Weber & Steitz, 1987), acrorepressor from phage λ (Andersonet al.1981), and the DNA-binding proteolytic fragment ofλcIrepressor protein (Pabo & Lewis, 1982) Although crystallographic studies of theE. coli lacrepressor protein were initiated as early as 1971 when it was the only regulatory protein available in sufficient quantities for structural studies (Steitzet al.1974), little was established about the structural aspects of DNA-binding proteins until the structure of CAP was determined in 1980 followed shortly thereafter by the structure ofλcrorepressor and subsequently that of the λ repressor fragment. There are now determined at high resolution the crystal structures of seven prokaryotic gene regulatory proteins or fragments [CAP,λcro,λcIrepressor fragment, 434 repressor fragment (Andersonet al.1987), 434crorepressor (Wolbergeret al.1988),E. coli trprepressor (Schevitzet al.1985),E. coli metrepressor (Raffertyet al.1989)],EcoRI restriction endonuclease (McClarinet al.1986), DNAse I (Suck & Ofner, 1986), the catalytic domain of γδ resolvase (Hatfullet al.1989) and two sequence-independent double-stranded DNA-binding proteins [the Klenow fragment ofE. coliDNA polymerase I (Olliset al.1985) and theE. coliHu protein (Tanakaet al., 1984)].