Integrated Calendar

A quarter of a century of modern structural bio-NMR has seen great progress in two intimately related research efforts, (i) development of methods for measuring NMR variables correlated with structure, and (ii) applying these to the structure determination of biologically relevant macromolecules. In this context the case of intrinsically disordered proteins (IDPs), flexible polypeptides quite prevalent in biological systems yet with no apparent structural features, has attracted much interest in the NMR community. This is due to the realization that, contrary to the structure-function dogma, they assume key biological roles, but more importantly because they cannot be studied by competing structural methods. This seminar will review the new techniques that have made IDPs accessible to NMR and describe our own recent contributions in utilizing temperature factors and scalar couplings to characterize these flexible polypeptides. Specifically, we have demonstrated for the disordered protein WIP, critical for cytoskeletal changes in activated T cells, that its free state is not quite as disordered as it may seem. In doing so, we highlight the unique abilities of NMR in addressing this intriguing class of proteins.