Structure and Dynamics of Biological Rotary Motors
We are studying the structure and molecular mechanism of biological rotary motors. Our current focus is on rotary A-type ATPases, which synthesize the biological energy carrier ATP in archaea and in certain eubacteria. Another project involves components of the bacterial flagellar motor. Both systems are very large and of highly dynamic and trans-membrane nature and hence require additional tricks and complementary techniques to obtain detailed structural information.
In both cases we use 3D reconstructions derived from electron micrographs of the intact protein complexes as low-resolution envelopes to fit higher resolution X-ray structures of individual subunits. This has allowed us to derive composite “atomic” models of the intact complexes. In addition we have obtained structures of individual components in different conformations. Supported by molecular dynamics simulations this has allowed us to obtain not only static 3D snapshots, but also information about the dynamics of the intact complexes that provide insights into their physiological role and regulation. Interestingly these intricate and highly optimized biological machines share common principles with machine elements of power generators or the internal combustion engine, such as pistons, crankshafts, pushrods and turbines and likewise require the right oil and fuel for optimal performance.
Daniela Stock was trained in mineralogy and crystallography at the University of Heidelberg and the Free University of Berlin, Germany. This was followed by a PhD with Robert Huber (Nobel Prize in Chemistry in 1988) at the Max-Planck Institute of Biochemistry, Martinsried, working on X-ray structures of 20S proteasomes and thermosomes and a postdoc with Sir JE Walker (Nobel Prize in Chemistry in 1997) at the MRC Laboratory of Molecular Biology in Cambridge, UK, working on the structure of yeast ATP synthase. In 2000 she started her independent lab at the MRC Laboratory of Molecular Biology working on X-ray structures of molecular machines.
She was involved in setting up a protein crystallization facility for the institute and performed pilot studies for an antibody facility, for which she developed domain antibody selection from phage display libraries using a membrane protein complex as antigen. In 2006 she was recruited to the Victor Chang Cardiac Research Institute to set up a new Structural Biology Laboratory equipped for high-throughput cloning, protein expression in bacterial, yeast and insect cells, protein purification (including membrane proteins and MDa sized molecular machines), domain antibody selection from phage display libraries, protein crystallization and X-ray structure determination using in house or synchrotron X-ray sources.