E0074

Unraveling the Mechanism of a Hexameric DNA Helicase. Tom Ellenberger, Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA

Helicases that unwind DNA ahead of the replication fork are hexameric enzymes that couple nucleotide hydrolysis with translocation and DNA strand separation. Crystal structures of the phage T7 DNA helicase reveal an arrangement of interlocked subunits in different conformations that are suggestive of a mechanism for movement of the ring shaped protein along DNA. Nucleotides bind at the subunit interface where an arginine from the neighboring subunit is positioned to contact the α-phosphate, perhaps serving to couple nucleotide hydrolysis with changes in conformation of the ring. Conserved motifs associated with DNA binding are located near the center of the ring. Deviations from six-fold symmetry, seen in a structure of T7 helicase determined by Dale Wigley and colleagues (Oxford University) are likely to control the activities of individual subunits and coordinate movement of this motor protein along DNA.