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Investigations of structural changes in the f1-subunit of adenosyltriphosphate synthase in the presence of different nucleotides and nucleotide analogs

Objective



Research objectives and content ATP is the universal energy currency of life. All living cells need ATP to maintain themselves, to move and to reproduce. Understanding the molecular mechanism by which ATP is synthesised is a major goal of modern biochemistry. ATP is synthesised by ATP-synthase which is a large, lollipop-shaped molecule found in all cells. Although it is known that the soluble part, F1 ATPase, is powered by electrochernical gradients in the cell, the precise way in which this molecular machine is able to synthesise ATP is not known. The recently solved crystal structure of the native enzyme suggests that it may act like a turbine, with the rotation (and attendant ATP-synthesis) being driven by changes in the structure of the molecule itself. My goal is to extend the existing structure to higher resolution and determine the high resolution crystal structures of conformational states of the F1-ATPase that are relevant to catalysis. This will be archived by co-crystallising the nucleotide free enzyme with nucleotides, nucleotide analogs and inhibitors which arrest the enzyme in a particular conformation. To obtain highest resolution possible, the data will be collected at liquid nitrogen temperature at high energy synchrotron sources. Training content (objective, benefit and expected impact) The objective of this project is to become more familiar with the methods involved in determination and refinement of macromolecular crystal structures. The benefit would be to be able to conduct independent research after finishing this training period. Structural biology is a modern and greatly expanding field that has a great demand for qualified scientist familiar with the latest technology. Links with industry / industrial relevance (22)

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

MRC Laboratory of Molecular Biology
Address
Hills Road
CB2 2QH Cambridge
United Kingdom