Grupo de Complejos Macromoleculares en la Respuesta a Daños en el DNA

Óscar Llorca Jefe de Grupo
T +34 (+34) 917 328 000 (Ext 3000)
ollorca@cnio.es

Investigadores

Javier Coloma
Ana I. Hernández
María Ibarra
Andrés López
Ángel Rivera
Marina Serna

Becarios Post-doctorales

Ana González
María Martínez

Becarios Pre-Doctorales

Natalia Cuervo
Carmen García
Nayim González

Our Group uses cryo-electron microscopy (cryoEM) to determine the 3D structure of large macromolecular complexes of relevance in cancer at high resolution. Structural information, in combination with molecular and cell biology and biochemistry, is then used to propose how these molecules work and increase our understanding of the molecular basis of cancer. Most of our efforts are currently focused on 2 major areas of research: the study of chaperones essential for the activation of several macromolecular complexes relevant in cancer such as those formed by the mTOR kinase, and the study of complexes implicated in the repair of DNA double-strand breaks. In addition, and in collaboration with other groups, we are studying the structure and mechanisms of several amino acid transporters.

Publicaciones

Coloma J, Gonzalez-Rodriguez N, Balaguer FA, Gmurczyk k, Aicart-Ramos C, Nuero OM, Luque-Ortega JR, Calugaru K, Lue NF, Moreno-Herrero F, Llorca O (2023). Molecular architecture and oligomerization of Candida glabrata Cdc13 underpin its telomeric DNA-binding and unfolding activity. Nucleic Acids Res 51, 668-686. Publicación CNIO.
Bragança Sara De, Aicart-Ramos Clara, Arribas-Bosacoma Raquel, Fortes P, Llorca O, Moreno-Herrero F (2023). APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining. Cell Reports 42, 111917. Publicación CNIO.
Serna M, González-Corpas A, Cabezudo S, López-Perrote A, Degliesposti G, Zarzuela E, Skehel JM, Muñoz J, Llorca O (2022). CryoEM of RUVBL1-RUVBL2-ZNHIT2, a complex that interacts with pre-mRNA-processing-splicing factor 8. Nucleic Acids Res 50, 1128-1146. Publicación CNIO. Open Access
Rivera-Calzada A, Arribas-Bosacoma R, Ruiz-Ramos A, Escudero-Bravo P, Boskovic J, Fernandez-Leiro R, Oliver AW, Pearl LH, Llorca O. (2022). Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.. Nat Commun 13, 7062. Publicación CNIO. Open Access
Rullo-Tubau J, Bartoccioni P, Llorca O, Errasti-Murugarren E, Palacín M. (2022). HATs meet structural biology. Curr Opin Struc Biol 74, 102389. Publicación CNIO.
Rivera Calzada A, Famelis Nikolaos, Llorca O, Geibel S (2021). Type VII secretion systems: structure, functions and transport models. Nat Rev Microbiol 19, 567-584. Publicación CNIO.
Unfried JP, Marín-Baquero M, Rivera-Calzada Á, Razquin N, Martín-Cuevas EM, de Bragança S, Aicart-Ramos C, McCoy C, Prats-Mari L, Arribas-Bosacoma R, Lee L, Caruso S, Zucman-Rossi J, Sangro B, Williams G, Moreno-Herrero F, Llorca O, Lees-Miller SP, Fortes P (2021). Long noncoding RNA NIHCOLE promotes ligation efficiency of DNA double-strand breaks in hepatocellular carcinoma.. Cancer Res 81, 4910-4925. Publicación CNIO.
Rodriguez CF, Escudero-Bravo P, Díaz L, Bartoccioni P, García-Martín C, Gilabert JG, Boskovic J, Guallar V, Errasti-Murugarren E, Llorca O, Palacín M (2021). Structural basis for substrate specificity of heteromeric transporters of neutral amino acids.. Proc Natl Acad Sci USA 118, e2113573118. Publicación CNIO.
Pal M, Muñoz-Hernandez H, Bjorklund D, Zhou L, Degliesposti G, Skehel JM, Hesketh EL, Thompson RF, Pearl LH, Llorca O, Prodromou C (2021). Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone. Cell Reports 36, 109317. Publicación CNIO.
Fresno C, García-Arriaza J, Martínez-Cano S, Heras-Murillo I, Jarit-Cabanillas A, Amores-Iniesta J, Brandi P, Dunphy G, Suay-Corredera S, Pricolo MR, Vicente N, López-Perrote A, Cabezudo S, González-Corpas A, LLorca O, Alegre-Cebollada J, Garaigorta U, Gastamiza P, Esteban M, Sancho D (2021). The Bacterial Mucosal Immunotherapy MV130 Protects Against SARS-CoV-2 Infection and Improves COVID-19 Vaccines Immunogenicity. Front Inmmunol 12, 748103. Publicación CNIO.
Dauden MI, López-Perrote A, Llorca O (2021). RUVBL1-RUVBL2 AAA-ATPase: a versatile scaffold for multiple complexes and functions. Curr Opin Struc Biol 19, 78-85. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO.
Rodríguez Carlos F, LLorca O (2020). RPAP3 C-Terminal Domain: A Conserved Domain for the Assembly of R2TP Co-Chaperone Complexes. Cells 9, E1139. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
Remacha L, Pirman D, Mahoney CE, Coloma J, Calsina B, Currás-Freixes M, Letón R, Torres-Pérez R, Richter S, Pita G, Herráez B, Cianchetta G, Honrado E, Maestre L, Urioste M, Aller J, García-Uriarte Ó, Gálvez MÁ, Luque RM, Lahera M, Moreno-Rengel C, Eisenhofer G, Montero-Conde C, Rodríguez-Antona C, Llorca Ó, Smolen GA, Robledo M, Cascón A (2019). Recurrent Germline DLST Mutations in Individuals with Multiple Pheochromocytomas and Paragangliomas. Am J Hum Genet 104, 651-664. Publicación CNIO.
Rivera-Calzada A, Carroni M (2019). Editorial: Technical Advances in Cryo-Electron Microscopy.. Front Mol Biosci 6, 72. Publicación CNIO. Open Access
Serna M (2019). Hands on Methods for High Resolution Cryo-Electron Microscopy Structures of Heterogeneous Macromolecular Complexes.. Front Mol Biosci 6, 33. Publicación CNIO. 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. Publicación CNIO. 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. Publicación CNIO. 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. Publicación CNIO.
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. Publicación CNIO.