People
Structural Biology Unit
Laboratory 4
We observe working molecular motors to understand their functioning. By means of cryo-electron microscopy we can obtain 3D maps of such motors under nearly physiological conditions, even within the cells. Our aim is to describe conformational changes of macromolecules while they perform their functions. We focus on motors involved in universal biological functions where interactions between protein and nucleic acids are essential. Structural studies of ribosomes during translation allow the understanding of the mechanisms which govern protein synthesis. In this process, interactions with translation factors and interference by several antibiotics are especially important. Another of our working interests concentrates on the structural characterization of p53 tumor suppressor. This protein works as transcription factor of genes involved in cell cycle control in vertebrates and hence functions as a tumor suppressor. The protein has been found mutated in about half of human tumors. We are interested in the structure of p53 tetramers and their interaction with DNA and other cell cycle controlling proteins.
- Dr Alan Fresht (Medical Research Council; University of Cambridge, Cambridge, UK).
- Dr Marina V. Rodnina (Max Planck Institute for Biophysical Chemistry, Göttingen, Germany).
- Dr Liang Tong (Columbia University, NY, USA).
Principal Investigator
Laboratory members
Publications
Roberto Melero, Sridharan Rajagopalan, Melisa Lázaro, Andreas C. Joerger, Tobias Brandt, Dmitry B. Veprintsev, Gorka Lasso, David Gil, Sjors H W Scheres, José María Carazo, Alan R Fersht and Mikel Valle; Electron microscopy studies on the quaternary structure of p53 reveal different binding modes for p53 tetramers in complex with DNA. Proc Natl Acad Sci USA 108, 2 557-562 (2011)
Ariel E. Mechaly, Augusto Bellomio, David Gil-Cartón, Koldo Morante, Mikel Valle, Juan Manuel González-Mañas, and Diego Guérin; Structural insights into the oligomerization and architecture of eukaryotic membrane pore-forming toxins. Structure 19, 181-191 (2011)
Olatz Landeta, Ane Landajuela, David Gil, Stefka Taneva, Carmelo DiPrimo, Begoña Sot, Mikel Valle, Vadim A. Frolov, and Gorka Basañez; Reconstitution of Proapoptotic BAK Function in Liposomes Reveals a Dual Role for Mitochondrial Lipids in the BAK-driven Membrane Permeabilization Process. Journal of Biological Chemistry 286, 10 8213-8230 (2011)
Mikel Valle; Almost lost in translation. Cryo-EM of a dynamic macromolecular complex: the ribosome. European Biophysics Journal 40, 5 589-597 (2011)
Lasso G, Yu LP, Gil D, Xiang S, Tong L, Valle M; Cryo-EM Analysis Reveals New Insights into the Mechanism of Action of Pyruvate Carboxylase. Structure 18, 10 1300-10 (2010)
L. Yu, S. Xiang, G. Lasso, D. Gil, M. Valle, L. Tong; A Symmetrical Tetramer for S. aureus Pyruvate Carboxylase in Complex with Coenzyme A. Structure 17, 6 823-832 (2009)
Scheres SH, Valle M, Grob P, Nogales E, and Carazo JM; Maximum likelihood refinement of electron microscopy data with normalization errors. Journal of Structural Biology 166, 2 234-240 (2009)
Scheres SH, Melero R, Valle M, and Carazo JM ; Averaging of Electron Subtomograms and Random Conical Tilt Reconstructions through Likelihood Optimization. Structure 17, 12 1563-1572 (2009)
Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, Elortza F, Lu SC, Mato JM, Falcon-Perez JM.; Characterization and Comprehensive Proteome Profiling of Exosomes Secreted by Hepatocytes.. J Proteome Res 7, 12 5157-5166 (2008)
Tidow, H., Melero, R., Mylonas, E., Freund, S. M., Grossmann, J. G., Carazo, J. M., Svergun, D. I., Valle, M., and Fersht, A. R.; Quaternary structures of tumor suppressor p53 and a specific p53-DNA complex. PNAS vol. 104 . no. 30, 12324-12329 (2007)
Scheres SH, Gao H, Valle M, Herman GT, Eggermont PP, Frank J, Carazo JM.; Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization. Nature Methods 4, 27-29 (2007)