Óscar Llorca Group Leader
T +34 (+34) 917 328 000 (Ext 3000)
ollorca@cnio.es

Our key mission is to provide in-depth structural and molecular understanding of how macromolecular complexes implicated in cancer work. This information is essential to comprehend why and how some proteins are involved in the development of cancer. This fundamental knowledge is the basis to start the search for potential strategies to interfere with the function of these macromolecules, either as therapeutic potential or research tool. To accomplish this, we make use of several biochemical and molecular biology tools in combination with cryo-electron microscopy (cryo-EM). Cryo-EM is used to visualise large macromolecular complexes, and to observe how they function. Two main objectives drive our current research: (i) the study of macromolecular complexes that function in the cellular response to DNA damage; and (ii) an HSP90 co-chaperone system implicated in the assembly, activation and regulation of several complexes that are essential for cancer progression. In addition, we also address other relevant questions for other human diseases, in collaboration with other groups.

Publications

• Rodríguez Carlos F, LLorca O (2020). RPAP3 C-Terminal Domain: A Conserved Domain for the Assembly of R2TP Co-Chaperone Complexes. Cells 9, E1139. CNIO Publication.
• López-Perrote A , NHug N, González-Corpas A, Rodríguez CF , Serna M, García-Martín C , Boskovic J, Fernandez-Leiro R, Caceres JF , Llorca O (2020). Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM. Elife 9, e63042. CNIO Publication.
• Dauden M, López-Perrote A, Llorca O (2020). RUVBL1–RUVBL2 AAA-ATPase: a versatile scaffold for multiple complexes and functions. Curr Opin Struc Biol 67, 78-85. CNIO Publication.
• Zimmermann F, Serna M, Ezquerra A, Fernandez-Leiro R, Llorca O, Luders J (2020). Assembly of the asymmetric human ?-tubulin ring complex by RUVBL1-RUVBL2 AAA ATPase. Sci Adv 6, eabe0894. CNIO Publication.
• Rodríguez CF, Pal M, Muñoz-Hernandez H, Pearl LH, Llorca O (2020). Modeling of a 14 kDa RUVBL2-Binding Domain with Medium Resolution Cryo-EM Density.. J Chem Inf Model 60, 2541-2551. CNIO Publication.
• Acebrón I, Righetto RD, Schoenherr C, Buhr S, Redondo P, Culley J, Rodríguez CF, Daday C, Biyani N, Llorca O, Byron A, Chami M, Gräter F, Boskovic J, Margaret C Frame, Stahlberg H, Lietha D (2020). Structural basis of Focal Adhesion Kinase activation on lipid membranes.. EMBO J 39, e104743. CNIO Publication.
• Famelis N, Rivera-Calzada A, Degliesposti G, Wingender M, Mietrach N, Skehel JM, Fernandez-Leiro R, Böttcher B, Schlosser A, Llorca O, Geibel S (2019). Architecture of the mycobacterial type VII secretion system. Nature 576, 321-325. CNIO Publication.
• Serna M (2019). Hands on Methods for High Resolution Cryo-Electron Microscopy Structures of Heterogeneous Macromolecular Complexes.. Front Mol Biosci 6, 33. CNIO Publication. Open Access
• Rivera-Calzada A, Carroni M (2019). Editorial: Technical Advances in Cryo-Electron Microscopy.. Front Mol Biosci 6, 72. CNIO Publication. Open Access
• Muñoz-Hernández H, Pal M, Rodríguez CF, Fernandez-Leiro R, Prodromou C, Pearl LH, Llorca O (2019). Structural mechanism for regulation of the AAA-ATPases RUVBL1-RUVBL2 in the R2TP co-chaperone revealed by cryo-EM. Sci Adv 5, eaaw1616. CNIO Publication. Open Access
• Menny A, Serna M, Boyd CM, Gardner S, Joseph AP, Morgan BP, Topf M, Brooks NJ, Bubeck D (2018). CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers. Nat Commun 9, 5316. CNIO Publication. Open Access
• Martino F, Pal M, Muñoz-Hernández H, Rodríguez CF, Núñez-Ramírez R, Gil-Carton D, Degliesposti G, Skehel JM, Roe SM, Prodromou C, Pearl LH, Llorca O (2018). RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex. Nat Commun 9, 1501. CNIO Publication. Open Access
• de Jorge EG, Yebenes H, Serna M, Tortajada A, Llorca O, de Córdoba SR (2018). How novel structures inform understanding of complement function. Semin Immunopathol 40, 3-14. CNIO Publication.
• Muñoz-Hernández H, Pal M, Rodríguez CF, Prodromou C, Pearl LH, Llorca O (2018). Advances on the Structure of the R2TP/Prefoldin-like Complex. Adv Exp Med Biol 1106, 73-83. CNIO Publication.
• Rivera-Calzada A, Mohinder P, Muñoz-Hernandez H, Luque-Ortega JR, Gil-Carton D, Degliesposti G, Skehel JM, Prodromou C, Pearl LH and Llorca O. (2017). The structure of the R2TP complex defines a platform for recruiting diverse client proteins to the HSP90 molecular chaperone system.. Structure 25, 1145-1152. Publication in other institutions.
• Subías Hidalgo M, Yébenes H, Rodríguez-Gallego C, Martín-Ambrosio A, Domínguez M, Tortajada A, Rodríguez de Córdoba S, Llorca O. (2017). Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications. Eur J Immunol 47, 504-515. Publication in other institutions.
• Huecas S, Ramirez-Aportela E, Vergoños A, Nuñez-Ramirez R, Llorca O, Diaz JF, Juan-Rodríuez J, Oliva MA, Castellen P, Andreu JM (2017). Self-Organization of FtsZ Polymers in Solution Reveals Spacer Role of the Disordered C-Terminal Tail.. Biophys J 113, 1831-1844. CNIO Publication.
• López-Perrote A, Harrison RE, Subías M, Alcorlo M, Rodríguez de Córdoba S, Morikis D, Llorca O. (2017). Ionic tethering contributes to the conformational stability and function of complement C3b.. Mol Immunol 85, 137-147. Publication in other institutions.
• Fernandez-Rodriguez C, Llorca O, Martino F (2017). Transmission Cryo-electron Microscopy in Drug Discovery.Royal Society of Biochemistry.. Biophysical Techniques in Drug Discovery (in press). CNIO Publication.
• Melero R, Hug N, López-Perrote A, Yamashita A, Cáceres JF, Llorca O (2016). The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation.. Nat Communications 7, 10585. Publication in other institutions.
• López-Perrote A, Castaño R, Melero R, Zamarro T, Kurosawa H, Ohnishi T, Uchiyama A, Aoyagi K, Buchwald G, Kataoka N, Yamashita A, Llorca O. (2016). Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex.. Nucleic Acids Res 44, 1909-1923. Publication in other institutions.