Structure and mechanism of multicomponent protein-nucleic acid assemblies. (360G-Wellcome-081916_Z_07_Z)

The research will focus on analysing protein-nucleic acid interactions and related molecular events in the framework of large assemblies. Although the main emphasis is on X-ray analysis, several complementary techniques such as electron microscopy, mass spectrometry and analytical ultracentrifugation, which provide insight into the assembly s composition and the strength of interaction, will be involved. Key goals in the main projects: (1) To understand the structure-function relationship for several tRNA modifying enzymes. To characterize protein interactions with tRNA and determine the crystal structures of protein-tRNA complexes by the X-ray analysis. (2) To continue investigations into the mechanism of DNA translocation by double-stranded DNA viruses, using bacteriophage SPP1 as a model system. Determine the X-ray structure of viral ATPase, which powers DNA translocation, and prepare stable complexes and obtain structural information for the complex of ATPase with the portal pr otein and DNA. Use the derived structural data for understanding how chemical events during the ATP hydrolysis are linked to the mechanical events during DNA translocation. (3) To extend studies on the regulatory processes involving multisubunit proteins and multiple-repeated RNA segments, using B.subtilis TRAP/RNA/anti-TRAP as a model system.