Exploring a Small Genome with Synchrotron Radiation: High-throughput Structural Studies of Thermotoga maritima

A. Deacon

Stanford Synchrotron Radiation Laboratory, SLAC, Stanford University, Stanford, CA 94309


Structural genomics aims to convert the ever-increasing supply of genomic sequence information into 3-dimensional protein structures. The Joint Center for Structural Genomics (JCSG) has adopted a strategy emphasizing technology development and miniaturization, as it attempts to fully automate each key step in its X-ray crystallography-based structure determination pipeline. Bioinformatics-based target selection; high-throughput protein expression and purification and nano-liter scale crystallization are all integral parts of this process. The Structure Determination Core of the JCSG is based at the Stanford Synchrotron Radiation laboratory and it is addressing the steps involved in fully automated crystal screening and quality assessment; rapid data collection; structure solution and refinement.

The JCSG has selected the 1877 open reading frames of the Thermotoga maritima genome as an initial set of targets, with which it can develop and test its technology pipeline. So far over 1500 crystals have been screened from approximately 150 targets and 29 structures have been solved. The first structures to emerge from the JCSG pipeline illustrate the power of the approach. Structures have been solved in a matter of hours and new protein folds have been discovered, which suggest new and unexpected catalytic mechanisms.

The JCSG is funded by the Protein Structure Initiative of the National Institutes of Health, National Institute of General Medical Sciences. SSRL operation is funded by DOE BES, and the SSRL Structural Molecular Biology program by DOE BER, NIH NCRR BTP and NIH NIGMS.



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