Structural Biology of Membrane Proteins, Macromolecular Assemblies and Viruses - Ben Hankamer

A/Prof Ben Hankamer

Determining the structures of membrane proteins, macromolecular assemblies and viruses is one of the great challenges of cell and structural biology. Using advanced high-resolution cryo-electron microscopes it is now possible to capture atomic-resolution information of biological macromolecules. However, as the captured images are inherently ‘noisy’, this information must be recovered by aligning many copies of the protein (~105-106 individual molecules) either computationally (by single particle analysis), or biochemically (via crystallography).

As part of the IMB’s Visible Cell® project we have established a powerful single particle analysis pipeline, as well as new biotechnologies for template assisted 2D crystal production. The single particle process involves merging large numbers of 2D projection images of randomly-oriented molecules to calculate 3D reconstructions. Our current benchmark resolution is ~10 Å at which individual α-helices begin to be resolved, and we are actively developing processes to improve this further. In parallel we have developed detergent-resistant 2D templates that chelate Ni at the surface, to facilitate the systematic production of 2D crystals of tethered His-tagged membrane proteins. Using these twin approaches we are studying a wide range of important membrane proteins (e.g. photosynthetic membrane protein complexes, ATPases, mechanosensitive channels), macromolecular assemblies (AAA ATPases and related proteins, ferritin, NS1) and icosahedral viruses. These structures provide fundamental new insights into many fascinating molecular machines and feed into the Visible Cell® project. These technologies are also being used to develop new bio-fuel production systems within the Solar Bio-fuels consortium.

The Solar Bio-fuels consortium, co-directed by Ben Hankamer, has brought together an international team of specialists to develop high-efficiency 2nd-generation bio-fuel production systems using microalgae. This represents a rapidly expanding area of biotechnology of global significance. Our specialisation is the structural biology and biochemistry of the photosynthetic machinery, which drives the first step of converting solar energy into chemical energy (fuels). Consequently its optimisation offers significant downstream benefits for all bio-fuel production systems (bio-ethanol, bio-diesel, BTL diesel, bio-H₂ and bio-methane). With colleagues, we are now taking the ‘Visible Cell®’ approach to develop a 3D atlas of the photosynthetic machinery within the cellular context. This 3D atlas will assist in the fine-tuning of the light capture and conversion processes of photosynthesis, just as a manual is required to tune the engine of a car.

Research Projects

• High-Resolution Single Particle Analysis: Biology, physics and software development


• The Visible Cell® Project: Resolving the 3D structure of the macromolecular assemblies


• Template mediated 2D crystallisation: Towards streamlined membrane protein crystallisation


• Second-generation micro-algal bio-fuel systems: Development of bio-fuels systems for bio-H₂, biodiesel and BTL-diesel production that are coupled to CO₂ sequestration

Key Publications

Pantelic, R.S., Lockett, L.J., Rothnagel, R., Hankamer, B., and Both, G. (2008). Cryo-electron microscopy map of Atadenovirus reveals cross-genus structural differences from human adenovirus. Journal of Virology 82: 7346-7356.

Mussgnug, J., Thomas-Hall, S., Rupprecht, J., Foo, A., Klassen, V., McDowall, A., Schenk, P., Kruse, O., and Hankamer, B. (2007). Engineering photosynthetic light capture: Impacts on improved solar energy to biomass conversion. Plant Biotechnology Journal 5: 802-814.

Woolford, D., Ericksson, G., Rothnagel, R., Muller, D., Landsberg, M., Pantelic, R., McDowall, A., Pailthorpe, B., Young, P., Hankamer, B., and Banks, J. (2007). Swarm(PS): Rapid, semi-automated single particle selection software. Journal of Structural Biology 157: 174-188.

Kruse, O., Rupprecht, J., Bader, K., Thomas-Hall, S., Schenk, P., Finazzi, G., and Hankamer, B. (2005). Improved photobiological H-2 production in engineered green algal cells. Journal of Biological Chemistry 280: 34170-34177.

Hankamer, B.D., Elderkin, S.L., Buck, M., and Nield, J. (2004). Organization of the AAA(+) adaptor protein PspA is an oligomeric ring. Journal of Biological Chemistry 279: 8862-8866.

Iwata, M., Imamura, H., Stambouli, E., Ikeda, C., Tamakoshi, M., Nagata, K., Makyio, H., Hankamer, B., Barber, J., Yoshida, M., Yokoyama, K., and Iwata, S. (2004). Crystal structure of a central stalk subunit C and reversible association/dissociation of vacuole-type ATPase. Proceedings of the National Academy of Science USA 101: 59-64.

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