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

Avoiding cancer requires active DNA repair mechanisms. In addition, tumour progression needs down-regulation of the cell response to DNA damage. Large and dynamic macromolecular complexes perform many of the activities of the DNA damage response. We cannot fully understand these biological reactions without understanding the structure of the participating molecules and how they interact. Our aim is to study the structural architecture of these large complexes and understand how they function. We are interested in several processes of relevance in cancer, including DNA repair, DNA damage signalling, DNA replication, and RNA quality surveillance mechanisms. We use cryo-Electron Microscopy (cryo-EM) as our main structural technique. Cryo-EM methods are revolutionising Biology and they are at the frontier of drug discovery. We can now explore the structure of complexes at close-to-atomic resolution by observing individual molecules in the electron microscope.

Publications

• RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.(2018)
  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
  Nat Commun 9, 1501-0.
• How novel structures inform understanding of complement function.(2018)
  de Jorge EG, Yebenes H, Serna M, Tortajada A, Llorca O, de Córdoba SR
  Semin Immunopathol 40, 3-14.
• Advances on the Structure of the R2TP/Prefoldin-like Complex.(2018)
  Muñoz-Hernández H, Pal M, Rodríguez CF, Prodromou C, Pearl LH, Llorca O
  Adv Exp Med Biol 1106, 73-83.
• CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.(2018)
  Menny A, Serna M, Boyd CM, Gardner S, Joseph AP, Morgan BP, Topf M, Brooks NJ, Bubeck D
  Nat Commun 9, 5316-.
• The structure of the R2TP complex defines a platform for recruiting diverse client proteins to the HSP90 molecular chaperone system.(2017)
  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.
  Structure 25, 1145-1152.
• Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications(2017)
  Subías Hidalgo M, Yébenes H, Rodríguez-Gallego C, Martín-Ambrosio A, Domínguez M, Tortajada A, Rodríguez de Córdoba S, Llorca O.
  Eur J Immunol 47, 504-515.
• Self-Organization of FtsZ Polymers in Solution Reveals Spacer Role of the Disordered C-Terminal Tail.(2017)
  Huecas S, Ramirez-Aportela E, Vergoños A, Nuñez-Ramirez R, Llorca O, Diaz JF, Juan-Rodríuez J, Oliva MA, Castellen P, Andreu JM
  Biophys J 113, 1831-1844.
• Ionic tethering contributes to the conformational stability and function of complement C3b.(2017)
  López-Perrote A, Harrison RE, Subías M, Alcorlo M, Rodríguez de Córdoba S, Morikis D, Llorca O.
  Mol Immunol 85, 137-147.
• Transmission Cryo-electron Microscopy in Drug Discovery.Royal Society of Biochemistry.(2017)
  Fernandez-Rodriguez C, Llorca O, Martino F
  Biophysical Techniques in Drug Discovery (in press).
• The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation.(2016)
  Melero R, Hug N, López-Perrote A, Yamashita A, Cáceres JF, Llorca O
  Nat Communications 7, 10585-.
• Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex.(2016)
  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.
  Nucleic Acids Res 44, 1909-1923.
• Amyloidogenesis of bacterial prionoid RepA-WH1 recapitulates dimer to monomer transitions of RepA in DNA replication initiation.(2015)
  Torreira E, Moreno-Del Álamo M, Fuentes-Perez ME, Fernández C, Martín-Benito J, Moreno-Herrero F, Giraldo R, Llorca O.
  Structure 23, 183-189.
• Structural insights on complement activation.(2015)
  Alcorlo M, López-Perrote A, Delgado S, Yébenes H, Subías M, Rodríguez-Gallego C, Rodríguez de Córdoba S, Llorca O.
  FEBS J 282, 3883-3891.
• Structure and Assembly of the PI3K-like Protein Kinases (PIKKs) Revealed by Electron Microscopy .(2015)
  Rivera-Calzada A et al. and Llorca O
  AIMS BIOPHYSICS 2, 36-57.
• Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD.(2014)
  Melero R, Uchiyama A, Castaño R, Kataoka N, Kurosawa H, Ohno S, Yamashita A, Llorca O.
  Structure 22, 1105-1119.
• Structure of Yin Yang 1 oligomers that cooperate with RuvBL1-RuvBL2 ATPases.(2014)
  López-Perrote A, Alatwi HE, Torreira E, Ismail A, Ayora S, Downs JA, Llorca O.
  J Biol Chem 289, 22614-22629.
• Structural basis for the stabilization of the complement alternative pathway C3 convertase by properdin.(2013)
  Alcorlo M, Tortajada A, Rodríguez de Córdoba S, Llorca O.
  Proc Natl Acad Sci USA 110, 13504-13509.
• Structural insights into nonsense-mediated mRNA decay (NMD) by electron microscopy.(2013)
  Llorca O
  Curr Opin Struc Biol 23, 161-167.