The Structural Biochemistry group investigates the molecular mechanisms, by which RNAs and proteins cooperate to bring about the biological functions of ribonucleoprotein complexes (RNPs; for an example see Figure). RNPs include some of the most complex macromolecular machineries of living cells, such as ribosomes and spliceosomes, which constitute fascinating objects to study the interplay of molecular conformation and biological function. Furthermore, RNPs act at the heart of numerous fundamental cellular processes, including virtually every aspect of gene expression and control. Finally, RNPs provide glimpses at the molecular ancestry of modern cells, which most likely evolved from an RNA-dominated world. Ultra-structural analysis of molecular RNP machines and their components using X-ray crystallography provides deep insights into their molecular mechanisms and suggests novel routes for their functional analysis.
Pena, V., Mozaffari Jovin, S., Fabrizio, P., Orlowski, J., Bujnicki, J.M., Lührmann, R., Wahl, M.C. (2009) Common design principles in the spliceosomal RNA helicase Brr2 and in the Hel308 DNA helicase. Mol. Cell 35, 454-466.
Luo, X., Hsiao, H.H., Bubunenko, M., Weber, G., Court, D. L., Gottesman, M.E. Urlaub, H., Wahl, M.C. (2008) Structural and functional analysis of the E. coli NusB-S10 transcription antitermination complex. Mol. Cell 32, 791-802.
Ganichkin, O., Xu, X.M., Carlson, B.A., Mix, H., Hatfield, D.L., Gladyshev, V.N., Wahl, M.C. (2008) Structure and catalytic mechanism of eukaryotic selenocysteine synthase. J. Biol. Chem. 283, 5849-5865.
Liu, S., Li, P., Dybkov, O., Nottrott, S., Hartmuth, K., Lührmann, R., Carlomagno, T. & Wahl, M. C. (2007) Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science 316, 115-120.
Diaconu, M., Kothe, U., Schlünzen, F., Fischer, N., Harms, J., Tonevitski, A.G., Stark, H., Rodnina, M.V., Wahl, M.C. (2005) Structural basis for the function of the ribosomal L7/12-stalk in factor binding and activation of GTP hydrolysis. Cell 121, 991-1004.
Wahl, M.C., Will, C.L., Lührmann, R. (2009) The spliceosome: Design principles of a dynamic RNP machine. Cell 136, 701-718