First steps towards effective methods in exploiting high-throughput technologies for the determination of human protein structures of high biomedical value.
Banci L., Bertini I., Cusack S., de Jong RN., Heinemann U., Jones EY., Kozielski F., Maskos K., Messerschmidt A., Owens R., Perrakis A., Poterszman A., Schneider G., Siebold C., Silman I., Sixma T., Stewart-Jones G., Sussman JL., Thierry JC., Moras D.
The EC 'Structural Proteomics In Europe' contract is aimed specifically at the atomic resolution structure determination of human protein targets closely linked to health, with a focus on cancer (kinesins, kinases, proteins from the ubiquitin pathway), neurological development and neurodegenerative diseases and immune recognition. Despite the challenging nature of the analysis of such targets, approximately 170 structures have been determined to date. Here, the impact of high-throughput technologies, such as parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens or the use of mass spectrometry to assist sample preparation, on the structural biology of mammalian protein targets is illustrated through selected examples.