It is becoming more and more evident that the cellular functions are performed by proteins that work in a coordinated manner to perform a given biological process in a more efficient manner. One of such processes is the protein folding pathway, controlled by a group of proteins termed molecular chaperones, which assist the folding of other proteins. We plan to study some of these chaperones, like the eukaryotic chaperonin CCT and different Hsp90, Hsp70, Hsp40 chaperones, using as a main tool electron microscopy and image processing.
These chaperones do not work alone and in many cases they function in a coordinated manner. Another objective is therefore the structural characterisation of the interaction between some of these chaperones, in particular the interaction between CCT and other chaperones such as prefoldin (PFD), the phosducin-like protein (PhLP), Hsp70, Hsp110, Hsp40,...
The centrosome is the major microtubule organising center (MTOC) in most animal cells. Typically, centrosomes are made of a pair of centrioles embedded in what classical electron-microscopy (EM) studies defined as "electron-dense" amorphous, pericentriolar material (PCM). Until now, not much structural information has been obtained, mostly because of the size and complexity of this organelle. We plan to study the overall structure of the centrosome using two approaches. The first one is electron tomography, a technique that has recently undergone major advances, and which may allow the structural characterization of entire centrosomes in condition close to the native state. The second approach is to use X-ray tomography, a technique which certainly allows the reconstruction of whole centrosomes, albeit at lower resolution than electron tomography. We plan to use the facilities set up at the dedicated beam line of the Spanish ALBA Synchrotron.
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José María Valpuesta |
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Jaime Martín-Benito |
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Post-doctoral investigators |
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Jorge Cuéllar |
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Begoña Sot |
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Elias Herrero |
Predoctoral students |
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Srdja Drakulic |
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Sara Alvira |
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Rocio Arranz |
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Lucia Quintana |
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Marina Serna |
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Marta Ukleja |
Technician |
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Ana Beloso |
- R. Arranz, G. Mercado, J. Martín-Benito, R. Giraldo, O. Monasterio, R. Lagos and J. M. Valpuesta (2012) “Structural characterization of microcin E492 amyloid formation: Identification of the precursors” J. Struct. Biol. (in press).
- A. Peña, K. Gewartowski, S. Mroczek, J. Cuéllar, A. Szykowska, A. Prokop, M. Czarnocki-Cieciura, J. Piwowarski, C. Tous, A. Aguilera, J. L. Carrascosa, J. M. Valpuesta* and A. Dziembowski* (2012) “Structural and biochemical characterisation of the THO complex reveals its architecture and mechanism of nucleic acids recognition” EMBO Journal 31, 1605-1616.
- S. Hormeño, B. Ibarra, Borja, J. M. Valpuesta, J. L. Carrascosa, J. R. Arias-Gonzalez “Mechanical stability of low-humidity single DNA molecules” (2012) Biopolymers 97, 199-208.
- M. Rodríguez-Rodríguez, M. A. Treviño, D.V. Laurents, R. Arranz, J.M. Valpuesta, M. Rico, M. Bruix and M.A. Jiménez (2011) “Characterization of the structure and self recognition of the human centrosomal protein NA14: Implications for stability and function” Protein Engineering, Design, and Selection 24, 883-892.
- R. Kumar, M. Ferez, M. Swamy, I. Arechaga, M. Rejas, J. M. Valpuesta, W. W. A. Schamel, B. Alarcon and H.M van Santen (2011) “Increased sensitivity of antigen-experienced T cells via enrichment for oligomeric TCR complexes” Immunity 35, 375-387.
- H. Yébenes, P. Mesa, I. G. Muñoz, G. Montoya and J. M. Valpuesta (2011) “Chaperonins: two rings for folding” Trends in Biochem. Sci. 6, 424-32. (cover of the issue).
- A.J. Martin-Galiano, M.A. Oliva, L. Sanz, A. Bhattacharyya, M. Serna, H. Yebenes, J.M. Valpuesta and J.M. Andreu (2011) “Bacterial Tubulin Distinct Loop Sequences and Primitive Assembly Properties Support its Origin from Eukaryotic Tubulin Ancestors” J. Biol. Chem. 286, 19789-19803.
- S. Hormeño, F. Moreno-Herrero, B. Ibarra, J.L. Carrascosa, J.M. Valpuesta and J.R. Arias-González (2011) “Condensation prevails over B-A transition in the global structure of DNA under low humidity conditions” Biophys. J. 100, 2006-2015.
- S. Hormeño, B. Ibarra, J.L. Carrascosa, J.M. Valpuesta, F. Moreno-Herrero, and J.R. Arias-Gonzalez (2011) “Mechanical properties of high G-C-content DNA with A-type base-stacking” Biophys. J. 100, 1996-2005.
- Y. Suk Lee, R. S. Smith, W. Hicks, B. King, J. M. Valpuesta, J. K. Naggert and P. M. Nishina (2011) “Prefoldin 5 is required for normal sensory and neuronal development in a murine model” J. Biol. Chem. 286, 726–736.
-A. Ionel, J. A. Velázquez-Muriel, D. Luque, J. R. Castón, A. Cuervo, A. Sali, J. M. Valpuesta, J. Martín-Benito and J. L. Carrascosa (2011) “Molecular rearrangements involved in capsid shell maturation of bacteriophage T7” J. Biol. Chem. 286, 234–242
- I. G. Muñoz^, H. Yébenes^, M. Zhou, P. Mesa, M. Serna, A.Y. Park, E. Bragado-Nilsson, A. Beloso, G. de Cárcer, M. Malumbres, C. V. Robinson, J. M. Valpuesta* and G. Montoya* “Crystal structure of the mammalian cytosolic chaperonin CCT in complex with tubulin” (2011) Nature Structural Molecular Biology 18, 14-9 (selected by the “Faculty of 1000”).
- M. Sakono, T. Zako, S. Drakulic, J. M. Valpuesta, M. Yohda and M. Maeda (2010) “Size-selective recognition of gold nanoparticles by a molecular chaperone” Chemical Physical Letters 501, 108-112.
- I. Arechaga, M. Swamy, D. Abia, W. Schamel, B. Alarcón and J. M. Valpuesta (2010) “Structural characterization of the T Cell Antigen Receptor complex by electron microscopy”. International Immunology 22, 897-903.
- Ramos, I., Martin-Benito, J., Finn, R., Bretaña, L., Aloria, K., Arizmendi, J.M., Ausió, J., A. Muga, Valpuesta, J.M.* and Prado, A* (2010) “Nucleoplasmin binds histone H2A-H2B dimers through its distal face” J. Biol. Chem. 285, 33771-33778.
- M. Moreno-del Álamo, A. Sánchez-Gorostiaga, A. M. Serrano, A. Prieto, J. Cuéllar, J. Martín-Benito, J. M. Valpuesta and R. Giraldo (2010) “The ISM Motif is the Main Target for Hsp70 Chaperones in the AAA+ Domain of Yeast Orc4p and Modulates Essential Interactions with Orc2p” J. Mol. Biol. 403, 24-39.
- A. Albert, C. Yunta, R. Arranz, A. Peña, E, Salido, J. M. Valpuesta and J. Martín-Benito (2010) “Structure of GroEL in Complex with an Early Folding Intermediate of Alanine Glyoxylate Aminotransferase.” J. Biol. Chem. 285, 6371-6376.
2011-2013. UE 262943-2 “MULTIFUN. Multifunctional Nanotechnology for selective detection and Treatment of Cancer”. 200000 €.
2011-2013. SEPAR Foundation “Ultraestructura de los complejos lipoproteicos del sistema surfactante pulmonar”. Investigador principal. 12000 €.
2011-2013. MICINN BFU2010-15703/BMC. “Chaperonas moleculares: una cadena de montaje involucrada en el plegamiento y degradacion de proteinas”. Investigador principal. 363.000 €.
2010-2013. CAM (S2009MAT-1507) “NOBIMAT-M. Nuevos materiales y dispositivos biofuncionales híbridos en Nanociencia” Investigador Principal del subproyecto. 829.000 €.
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