个人简介

Ph.D. (1981) University of Pennsylvania

研究领域

Biochemistry

DYNAMICS STRUCTURE AND FUNCTION OF MEMBRANE PROTEINS BY SOLID STATE NMR In this laboratory we bring together skills in nuclear magnetic resonance (NMR) spectroscopy, membrane and computational biophysics, and biomathematics. These latter skills are brought to the lab through a close collaboration with Professor Jack Quine of the FSU Department of Mathematics. Our goal is to characterize the structure and dynamics of membrane proteins for understanding molecular function; in particular we are interested in cation channels. Membrane proteins represent a major challenge for structural biology. Very few structures have been obtained to date, but new methods such as solid state NMR have the potential to be an important technology, complementary to solution state NMR and x-ray crystallography for solving these important drug targets. In previous studies of the channel-forming polypeptide gramicidin A, we have described detailed functional principles that influence conductance efficiency and conductance specificity. To obtain information for membrane proteins, this laboratory is a world leader in the development of solid-state NMR techniques for structural and dynamic characterizations. Through the use of lipid bilayer preparations that are uniformly aligned with respect to the magnetic field of the NMR spectrometer, it is possible to obtain high-resolution spectra without the required presence of isotropic motions. Indeed for these structural characterizations there is no molecular weight limit, as there is for solution-state NMR spectroscopy. Today this approach has been demonstrated with the three-dimensional structural characterization of gramicidin in a lipid bilayer environment. This now represents the highest resolution structure of a protein or peptide in such an environment that has been deposited in the Protein Data Bank. Currently, we are working on several membrane proteins. The M2 protein from influenza A virus forms a H+ channel and is a key functional protein in flu infections. Here, our goal is to obtain a complete three-dimensional structure. Another project involves the KcsA K+ channel from Streptomyces lividans. It is the first x-ray crystal structure of a cation channel and we are interested in refining the structural detail along the cation channel in this medium-resolution crystal structure. We are also working on lac permease, a sugar transporter from E. coli. This very large protein has not been crystallizable, and we are developing novel approaches for obtaining structural information.

近期论文

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Hu J, Qin H, Gao FP, Cross TA. A systematic assessment of mature MBP in membrane protein production: overexpression, membrane targeting and purification. Protein Expr Purif. 2011, Nov;80(1), 34-40 Separovic F, Killian JA, Cotten M, Busath DD, Cross TA. Modeling the membrane environment for membrane proteins. Biophys J. 2011, Apr 20;100(8), 2073-4 Peterson E, Ryser T, Funk S, Inouye D, Sharma M, Qin H, Cross TA, Busath DD. Functional reconstitution of influenza A M2(22-62). Biochim Biophys Acta. 2011, Feb;1808(2), 516-21 Sharma M, Yi M, Dong H, Qin H, Peterson E, Busath DD, Zhou HX, Cross TA. Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer. Science. 2010, Oct 22;330(6003), 509-12