Abstract
The X-ray structure of a ternary complex of Negative Cofactor 2 (NC2), the TATA box binding protein (TBP), and DNA has been determined at 2.6 Å resolution. The N termini of NC2 α and β resemble histones H2A and H2B, respectively, and form a heterodimer that binds to the bent DNA double helix on the underside of the preformed TBP-DNA complex via electrostatic interactions. NC2β contributes to inhibition of TATA-dependent transcription through interactions of its C-terminal α helix with a conserved hydrophobic feature on the upper surface of TBP, which in turn positions the penultimate α helix of NC2β to block recognition of the TBP-DNA complex by transcription factor IIB. Further regulatory implications of the NC2 heterodimer structure are discussed.