Fast Multidimensional NMR Spectroscopy: From protein structures to nanotubes

ABSTRACT:

NMR spectroscopy has undergone a revolution in recent years with the advent of several new methods overcoming the problems of sensitivity and resolution. Our research has focused on developing novel methods in solution and solid-state NMR to unravel structural, dynamic and functional roles of biomolecules in high-resolution. Several new experiments have been designed which facilitate data acquisition faster by more than an order of magnitude over conventional approaches. These methods have been applied to different biological systems. One of them involves insulin-like growth factor binding proteins (IGFBPs), a family of 6 homologous proteins about 30 kDa in size and implicated in different types of cancers. IGFBPs bind insulin-like growth factors (IGF) strongly and regulate the activity of the latter. Using IGFBP-2 as a model system, our goal is to structurally characterize the various IGF-IGFBP interactions at an atomic level. We recently discovered that a C-terminal fragment of IGFBP-2 self-assembles spontaneously and reversibly into soluble nanotubular structures several micrometers long via a mechanism involving inter-molecular disulphide bonds and exhibiting enhanced fluorescence. The principle of fast NMR methods and their application to the different biological systems alluded to above will be presented.