Dr Daniela Stock, PhD
Laboratory Head, Structural and Computational Biology Division
Telephone: +61-2-9295 8660
Research Focus:
Our lab uses X-ray crystallography to determine the structure of proteins and protein complexes at high resolution. We are currently focussed on determining the structure and function of protein complexes that contain molecular rotary motors such as vacuolar ATPases and the flagellar motor. Both complexes are involved in proton translocation through membranes and we are investigating the overall architecture of the proton channels, the molecular mechanisms of proton translocation and the generation of rotation. By comparing two very different systems, we are hoping to discover some of the general principles of biological rotary motors.
Structure and function of A- and V-type ATPases
F-, V-, and A-type ATPases are central to biological energy conversion. Photosynthetic and respiratory systems of all living organisms convert energy derived from light or nutrients into transmembrane electrochemical proton gradients. F-type ATP synthases use energy stored in these gradients to synthesise the universal biological energy carrier ATP from ADP and inorganic phosphate.
Eukaryotic vacuolar ATPases (V-ATPases) are related proton pumps that are specialised in proton transfer across the membranes of eukaryotic cells. Defects in both ATPases lead to serious genetic disorders, like Batten disease, osteopetrosis and cardiomyopathies to name but a few.
While eukaryotic V-ATPases have highly complex and fragile structures, A-ATPases that occur in the membranes of archaea and certain bacteria are more amenable for structural research. Though simpler by design, they are more versatile than their eukaryotic counterparts in that they can act both as ATP synthases and as proton pumps.
We are currently using a combination of electron microscopy and X-ray structural approaches to obtain pseudo-atomic structures of these ATPases. This will allow insights into the molecular mechanisms of proton translocation and the generation of motion and will be instrumental for drug development.
Future Plans
We have recently relocated to the Victor Chang Cardiac Research Institute. In future our aim is to become more involved in structure determinations of proteins of cardiologic interest with an emphasis on membrane proteins. We are currently setting up crystallisation and X-ray facilities to support crystallographic aspects of cardiology at the Victor Chang. Applications from highly motivated individuals at all career levels are welcome. Please send inquiries including cv to Dr Daniela Stock.
Links:
VCCRI Structural Biology Homepage http://www.proteinstructure.org.au
Co-Investigators:
Mike Ginsburg, BSc, MESc
Ricardo Bernal,
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Jan Lowe, Daniela Stock, Bing Jap, Peter Zwickl, Wolfgang Baumeister & Robert Huber. Crystal Structure of the 20S Proteasome from the Archaeon T. acidophilum at 3.4A Resolution. Science 1995; 268: 533-539.
Daniela Stock, Lars Ditzel, Wolfgang Baumeister, Robert Huber & Jan Lowe. The Catalytic Mechanism of the 20S Proteasome of Thermoplasma acidophilum revealed by X-ray Crystallography.
Daniela Stock,
Michael Groll, Lars Ditzel, Jan Lowe, Daniela Stock, Matthias Bochtler, Hans D. Bartunik & Robert Huber. Structure of 20S proteasome from yeast at 2.4A resolution. Nature. 1997; 386: 463-471.
Lars Ditzel, Jan Lowe, Daniela Stock, Karl-Otto Stetter, Harald Huber, Robert Huber & Stefan Steinbacher. Crystal Structure of the Thermosome, The Archaeal Chaperonin and Homologue of CCT. Cell 1998; 93: 125-138.
Daniela Stock, Andrew G. W. Leslie & John E. Walker. Molecular Architecture of the Rotary Motor in ATP Synthase. Science 1999; 286: 1700-1705.
Daniela Stock,
A. Chapin Rodriguez & Daniela Stock. Crystal structure of reverse gyrase: insights into the positive supercoiling of DNA. EMBO J. 2002; 21: 418-426.
M. Kampmann & Daniela Stock. Reverse gyrase has heat-protective DNA chaperone activity independent of supercoiling. Nucleic Acids Research 2004; 32: 3537-3545.
Ricardo A. Bernal & Daniela Stock. Three Dimensional Structure of the Intact Thermus thermophilus H+-ATPase/Synthase by Electron Microscopy. Structure 2004; 12: 1789-1798.
Daniela Stock, Olga Perisic & Jan Lowe. Robotic nanolitre protein crystallisation at the MRC Laboratory of Molecular Biology. Progress in Biophysics and Molecular Biology 2005; 88: 311-327.
Ingmar Schafer, Susanne M. Bailer, Monika G. Duser, Michael Borsch, Ricardo A. Bernal, Daniela Stock & Gerhard Gruber. Crystal Structure of the Archaeal A1AO ATP Synthase Subunit B from Methanosarcina mazei Go1: Implications of Nucleotide-binding Differences In the Major A1AO Subunits A and B. J. Mol. Biol. 2006; 358: 725-740.
Olga Esteban, Ricardo A. Bernal, Mhairi Donohoe, Hortense Videler, Michal Sharon, Carol V. Robinson & Daniela Stock. Stoichiometry and localisation of the stator subunits E and G in T. thermophilus H+ ATPase/synthase. J. Biol. Chem. 2008; 283: 2595-2603.
Lawrence K. Lee*, Alastair G. Stewart*, Mhairi Donohoe, Richardo A. Bernal & Daniela Stock (2010) The structure of the peripheral stalk of T. thermophilus H+- ATPase/synthase. Nat. Struct. Mol. Bol. 17, 373-378. *authors contributed equally.
Lawrence K. Lee, Michael Ginsburg, Claudia Crovace, Mhairi Donohoe & Daniela Stock. The structure of the torque ring of the flagellar motor and the molecular basis for rotational switching. Nature accepted in principle subject to editorial changes.
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