Macromolecular Architecture and Function Group

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

Research Scientists

Javier Coloma
Ana I. Hernández
Ángel Rivera

Post-Doctoral Fellows

Jaime Louro
Ana González
María I. Daudén
Andrés López
María Martínez
Clara Reglero
Aarón Terán

Graduate Students

Carmen García
Nayim González
Álvaro López
Juan Tasis
Celia Varela

Our research aims to visualise the three-dimensional architecture of large macromolecular complexes that play critical roles in cancer biology using cryo-electron microscopy (cryo-EM). By integrating structural insights with molecular biology, cell biology, and biochemistry, we reveal how these complexes function and drive cancer-related pathways. Current efforts focus on two areas: chaperones that activate assemblies such as mTORC1—a key regulator of cell growth and metabolism—and the study of DNA repair and genome stability complexes, which safeguard genetic integrity and whose malfunction underlies tumour development. In collaboration with other groups, we also explore the mechanisms of microtubule nucleation that orchestrate mitotic spindle assembly during cell division, a process fundamental to both normal proliferation and oncogenesis. Our ultimate goal is to generate mechanistic knowledge and a deeper understanding of biological processes relevant to cancer biology.

Recent publications

López-Perrote A, Martín-Cuevas EM, Mérida-Cerro JA, Aicart-Ramos C, González-Corpas A, González J, Le Coq J, Boskovic J, Chillón I, Llorca O, Moreno-Herrero F, Huarte M. (2026). CONCR lncRNA organizes a 3′-end structural domain that engages DDX11 for DNA replication and sister chromatid cohesion. Mol Cell (in press). CNIO Publication.
Serna M, Brito C, Speroni S, Zimmermann F, Lopez-Perrote A, Gili M, Lacasa C, Lüders J, Surrey T, Llorca O. (2026). Structural basis of human γTuRC closure during CM1-activated microtubule nucleation. Nat Commun (in press). CNIO Publication.
Calugaru K, Yu EY, Huang S, González-Rodríguez N, Coloma J, Lue NF. (2025). The yeast CST and Polα/primase complexes act in concert to ensure proper telomere maintenance and protection. Nucleic Acids Res 53, gkaf245. CNIO Publication.
Palacios-Abella A, López-Perrote A, Boskovic J, Fonseca S, Úrbez C, Rubio V, Llorca O, Alabadí D. (2025). The structure of the R2T complex reveals a different architecture from the related HSP90 cochaperone R2TP. Structure 33, 740-752. CNIO Publication.
González-Rodríguez N, Chacón-Sánchez C, Llorca O, Fernández-Leiro R. (2025). Automated and modular protein binder design with BinderFlow. PLoS Comput Biol 21, e1013747. CNIO Publication.
Cabezudo S, Cuervo N, García-Martín C, López-Perrote A, Reglero C, Maqueda-Real A, González-Corpas A, Serna M, Megías D, Efeyan A, Park S, Llorca O. (2025). Characterization of WAC interactions with R2TP and TTT chaperone complexes linking glucose and glutamine availability to mTORC1 activity. FEBS Open Bio 15, 1771-1788. CNIO Publication.
Fort J, Nicolàs-Aragó A, Maggi L, Martinez-Molledo M, Kapiki D, González-Novoa P, Gómez-Gejo P, Zijlstra N, Bodoy S, Pardon E, Steyaert J, Llorca O, Orozco M, Cordes T, Palacín M. (2025). The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters. PNAS Nexus 4, pgae584. CNIO Publication.
Brito C, Serna M, Guerra P, Llorca O, Surrey T. (2024). Transition of human γ-tubulin ring complex into a closed conformation during microtubule nucleation. Science 383, 870-876. CNIO Publication.
Rullo-Tubau J, Martinez-Molledo M, Bartoccioni P, Puch-Giner I, Arias Á, Saen-Oon S, Stephan-Otto Attolini C, Artuch R, Díaz L, Guallar V, Errasti-Murugarren E, Palacín M, Llorca O. (2024). Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter. Nat Commun 15, 2986. CNIO Publication. Open Access
Serna M, Zimmermann F, Vineethakumari Ch, Gonzalez-Rodriguez N, Llorca O, Lüders J (2024). CDK5RAP2 activates microtubule nucleator gTuRCby facilitating template formation and actin release. Dev Cell 59, 3175-3188. CNIO Publication.
García- Martín C, López-Perrote A, Boskovic J , Llorca O (2024). Mechanism of allosteric inhibition of RUVBL1-RUVBL2 ATPase by the small molecule CB-6644. Cell Rep Phys Sci 5, 101982. CNIO Publication.
López-Perrote A, Serna M, Llorca O. (2024). Maturation and Assembly of mTOR Complexes by the HSP90-R2TP-TTT Chaperone System: Molecular Insights and Mechanisms. Subcell Biochem 104, 459-483. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication. 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. CNIO Publication. 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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication.