Lorne Protein: A synch for protein research

Over the next few days, we'll continue to preview the 2004 Lorne conferences: Protein, Cancer and Genome.

Desirable accessories for very shiny new national synchrotron, option #7: synchrotron radiation circular dichroism (SRCD) spectroscope, perfect for determining secondary protein structure and observing dynamics of protein folding.

With Australia's national synchrotron now under construction near Monash University, SRCD expert Bonnie Wallace should have an attentive audience when she describes her research at the 2003 Lorne Protein Conference in February.

The US-born, Yale-educated researcher, now professor of molecular biophysics at the University of London, has a laboratory at the Daresbury Synchrotron in Cheshire, where she has been harnessing the latest wrinkle -- more accurately, a double-twist -- in the spectroscopic analysis of proteins.

Circular dichroism spectroscopy measures the differential absorption of left- and right-handed, circularly polarised light by protein molecules as a function of the wavelength of the incident radiation -- in this case, ultraviolet (UV) radiation, rather than X-rays.

Today's commercial CD spectroscopes use xenon lamps, which can only generate UV wavelengths between about 190 and 300 nanometres. Synchrotron radiation is much brighter, and extends the wavelength range to between 160 and 300 nanometres -- the range most useful for studying proteins and DNA.

Wallace says biological macromolecules such as proteins and DNA are composed of optically active elements with distinctive three-dimensional structures: helixes, sheets, turns and coils. Each element absorbs UV radiation in a characteristic pattern that varies with wavelength.

The molecule's specific combination of these secondary structural elements yields a yields a unique CD absorption 'fingerprint' from which the researcher can mathematically extract details of the molecule's structure.

SRCD can also be used to study the dynamics of protein folding, and conformational changes in response to environmental influences, including binding reactions with drug molecules.

Influential

Wallace will also describe her use of SRCD spectroscopy to investigate the structure and dynamics of membrane proteins and signalling polypeptides at a membrane protein workshop at the Walter and Eliza Hall Institute on Friday, February 6.

She has been using SRDC to investigate the structure and dynamics of ion channels in membranes, including sodium and calcium channels, and unusual antibiotic peptides called tricotoxins and peptabiols, that form ion channels.

Wallace's work has been influential in the decision to install an SRCD spectrometer on a beamline on Britain's new Diamond synchrotron.

Apart from Daresbury, only two other synchrotrons in the world -- one in Denmark, the other at the Brookhaven National Laboratory in the US -- currently have SRCD facilites. "Melbourne is thinking about one, along with Germany, China, Japan, France and Brazil," Wallace says.