SOLUTION STRUCTURE OF THE CELLULAR FACTOR BAF RESPONSIBLE FOR PROTECTING RETROVIRAL DNA FROM AUTOINTEGRATION

The solution structure of the human barrier-to-autointegration factor, BAF, a 21,000 M, dimer, has been solved by NMR, including extensive u se of dipolar couplings which provide a priori long range structural i nformation. BAF is a highly evolutionarily conserved DNA binding prote in that is responsible for inhibiting autointegration of retroviral DN A, thereby promoting integration of retroviral DNA into the host chrom osome. BAF is largely helical, and each subunit is composed of five he lices. The dimer is elongated in shape and the dimer interface compris es principally hydrophobic contacts supplemented by a single salt brid ge. Despite the absence of any sequence similarity to any other known protein family, the topology of helices 3-5 is similar to that of a nu mber of DNA binding proteins, with helices 4 and 5 constituting a heli x-turn-helix motif. A model for the interaction of BAF with DNA that i s consistent with structural and mutagenesis data is proposed.