Small no longer means impossible – new technique enables study of ‘challenging’ proteins
14 November 2011
Researchers from Hull, Bristol and Frankfurt have shown that a new technique for identifying molecular structure can be used effectively on small samples of biological proteins, particularly proteins that are targeted for drug development.
The technique, an enhanced form of nuclear magnetic resonance (NMR) spectroscopy, could enable the structure of a protein to be identified within hours, rather than weeks or months, radically speeding up the process of drug discovery. The research was funded by BBSRC amongst others and the findings are published online in the Journal of the American Chemical Society.
Dr Mark Lorch from the University of Hull, who led the research, explains: "Membrane proteins are important targets for the pharmaceutical industry, but they're very difficult to create in large quantities. For some, NMR isn't feasible at all, but even when it is, only small amounts of data can be gained from each small sample, which makes the whole process of identifying the structure very time consuming and expensive.
"Using this technique, we were able to get significant structural data from a small sample of a protein in just 20 hours of NMR time. This is the first time the technique has been shown to work on the size of sample that can be realistically created from any biological protein."
The researchers, from the Universities of Hull, Bristol and Goethe University, used a method known as dynamic nuclear polarisation (DNP), which boosts the number of nuclei that can be measured through NMR and so increases the signal picked up from the protein.
Although DNP has been used before on large sample sizes of well-studied proteins, the researchers are the first to show its effectiveness in studying a more challenging protein, opening the door to the study of biological samples that are currently inaccessible to conventional NMR.
The study focused on the Sec translocon protein, which transports other proteins either across or into biological membranes. This process is triggered when a signal peptide called LamB binds with Sec translocon and the researchers wanted to identify structural information on how the two interact. This would have been impossible through traditional NMR, as the signal peptide makes up such a small part of the sample to be studied. However, using DNP to enhance the signal from the peptide, the researchers were able to get significant information in a very short period of time.
The work was carried out at the European Centre of Biomolecular Magnetic Resonance (BMRZ) in Frankfurt and was funded through the European Union and the Biotechnology and Biological Sciences Research Council (BBSRC).
Notes to editors
Mark Lorch is an RCUK Fellow in the University of Hull's Department of Chemistry. His co-researchers were: Ian Collinson, Department of Biochemistry, University of Bristol, Lenica Reggie, Jakob J. Lopez and Clemens Glaubitz, Institute for Biophysical Chemistry and Centre for Biomolecular Magnetic Resonance (BMRZ), Goethe University.
About Health research at the University of Hull
Health-related research at the University of Hull ranges from biology and biochemistry to sports science, psychology and medicine. The University heads major UK and EU clinical trials into heart disease, dementia care, obesity and nutrition and is a recognised centre for research into head and neck cancers, medical imaging, respiratory diseases and remote monitoring of health conditions (telehealth).
Health research at the University of Hull is highly translational, with strong links between fundamental scientists and clinicians ensuring maximum impact on treatment and practice. The University has a joint medical school with the University of York. Hull York Medical School (HYMS) works closely with regional NHS trusts and trains 130 new doctors each year.
In the 2008 national Research Assessment Exercise (RAE), 80% of the University's research across all fields was judged to be of international standard in terms of originality, significance and rigour. The National Student Survey (NSS) consistently ranks the University in the top ten mainstream English Universities. For more information visit: www.hull.ac.uk.
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Funded by Government, and with an annual budget of around £445M, we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.