Structural Genomics
Using Synchrotron X-ray Protein Crystallography
 
The recent progress of the human and other genome sequencing projects has produced a tremendous amount of genetic information on the entire genomes. Subsequently, new scientific branches called post-genomic sciences started to take best advantage of the genome information and to use it to improve human life.
 
Proteins are the products of genes and they perform numerous functions in cells through intricate interplay between their amino acid residues and other molecules. Therefore, one important aspect of the post-genomic sciences is to study the network of proteins and other biological molecules. Here, elucidation of three-dimensional structures of proteins and their complexes is the key to fully understand their functions. Traditionally, structural biologists have been studying functions of specific proteins and nucleic acids of their interest using X-ray crystallography and/or nuclear magnetic resonance (NMR) techniques. In contrast, structural genomics (SG) is an endeavor to determine protein structures en masse in a systematic way, thus expected to play a major role in post-genomic sciences. The advancement in the past ten years at modern synchrotron radiation facilities has revolutionized the protein crystallography field. Highly collimated and energy-tunable X-ray photons from synchrotron beam lines have reduced the amount of time required for accurate structure determination by one to two orders of magnitude and made it possible to determine very large protein structures from extremely small crystals.
 
Combined with the technological advancements of genome analyses and proteomics, a science to study interaction of network of proteins, it is now foreseeable to solve thousands of protein structures and analyze their functions in a coordinated way worldwide. Clearly, the synchrotron radiation is indispensable for the SG projects. In this article, I will describe an example of SG project with specific biological targets and development of new X-ray crystallography techniques for highly efficient structure determination.