On NMR-based structural proteomics

NMR spectroscopy plays an important role in the derivation of the atomic resolution structures of soluble proteins in structural proteomics projects because NMR neatly complements X-ray crystallography: 1) many proteins do not form diffraction quality crystals and their structures are thus amenable to determination solely by NMR;2) the success of structural determination by NMR and X-ray, i.e., the quality of NMR spectra and crystallization success, are hardly correlated; 3) the cost-effectiveness of NMR and X-ray crystallographic structure production is nowadays comparable and 4) NMR is about equally successful for pro- and eukaryotic proteins, while eukaryotic proteins crystallize less frequently than prokaryotic proteins. Since the inception of structural proteomics around the year of 2000, all components required for high-throughput NMR structure production of soluble proteins were established or developed further. Currently, about 10% of the soluble protein structures solved in the framework of the US Protein Structure Initiative are obtained by using NMR. Apart from contributing novel structures to accomplish "structural coverage" of families of sequence homologs, many of these NMR structures are of immediate importance for biomedical and biological research. More recently, projects focusing on methodology development for NMR-based structural proteomics of (integral) membrane proteins were also established. In general, the methodology developed for structural proteomics projects nowadays broadly impacts on the scientific infrastructure of NMR-based structural biology.