University of Illinois at Urbana-Champaign
Research in the Rienstra group aims to establish solid state nuclear magnetic resonance (SSNMR) as a preferred method for routine, atomic resolution structural and dynamic analysis of biological macromolecules. The field of SSNMR is in the midst of a revolution not unlike the advances in X-ray crystallography that occurred during the 1970’s, and solution NMR in the 1980’s. Those methods have been responsible for the vast majority of all protein structures known to date. However, neither method has been applied in a general fashion to membrane proteins and protein-lipid complexes, which have profound importance to biochemistry, yet remain vastly underrepresented in the database of known protein structures. SSNMR has two distinct advantages relevant to the study of biological membranes. First, unlike in solution NMR, where global correlation (tumbling) times impose fundamental restrictions of the particle size that may be studied, in the solid state, spectral intensities and homogeneous line widths of individual NMR signals do not depend upon molecular weight. Second, unlike in crystallography, in our SSNMR experiments long-range order is not required, because the inhomogeneous line widths are determined by the degree of order in the local (5 to 10 Å) environment; therefore heterogeneous sample environments (e.g., asymmetric oligomeric assemblies, protein-lipid complexes, etc.) are inherently no less qualified for structural analysis by SSNMR than single crystals. These two characteristics make SSNMR the best (and often the only) method for studying atomic resolution structure in biological membranes, precipitated peptide aggregates (e.g., β-amyloid peptides), glasses, frozen solutions and lyophilized powders (e.g., trapped enzyme-substrate intermediates). Therefore intense interest has been focused on the problem of global structure determination by SSNMR.