Inés Muñoz Head of Unit
T +34 917328000 (Ext 3020)
imunoz@cnio.es

The Crystallography and Protein Engineering Unit (XTPEUnit) is a central core facility as well as a research laboratory; its main goal is to fulfil the requests of research groups at the CNIO and outside our Centre, by providing on-demand services at different levels. These services range from the production of recombinant proteins for different types of biochemical/biophysical assays and monoclonal antibody production, to macromolecular structural determination at low resolution by small-angle X-ray scattering (SAXS), or at high resolution by X-ray crystallography. The latter includes co-crystallisation in the presence of inhibitors, during the guided drug design process.

Publications

• Intratumoral expression using a NFkB-based promoter enhances IL12 antitumor efficacy(2019)
  Garaulet G, Pérez-Chacon G, Alarcón H, Alfranca A, Mulero F, Martínez-Torrecuadrada J, Zapata JM, Rodríguez A
  Cancer Gene Ther (in press).
• Pancreatic Tumor Microenvironment Modulation by EphB4-ephrinB2 Inhibition and Radiation Combination(2019)
  Lennon S, Oweida A, Milner D, Phan AV, Bhatia S, Van Court B, Darragh L, Mueller AC, Raben D, Martínez-Torrecuadrada JL, Pitts TM, Somerset H, Jordan KR, Hansen KC, Williams J, Messersmith WA, Schulick RD, Owens P, Goodman KA, Karam SD
  Clin Cancer Res (in press).
• Exome Sequencing of Plasma DNA Portrays the Mutation Landscape of Colorectal Cancer and Discovers Mutated VEGFR2 Receptors as Modulators of Antiangiogenic Therapies(2018)
  Toledo RA, Garralda E, Mitsi M, Pons T, Monsech J, Vega E, Otero Á, Albarran MI, Baños N, Durán Y, Bonilla V, Sarno F, Camacho-Artacho M, Sanchez-Perez T, Perea S, Álvarez R, De Martino A, Lietha D, Blanco-Aparicio C, Cubillo A, Domínguez O, Martínez-Torrecuadrada JL, Hidalgo M
  Clin Cancer Res 24, 3550-3559.
• MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management(2018)
  Morcillo MÁ, García de Lucas Á, Oteo M, Romero E, Magro N, Ibáñez M, Martínez A, Garaulet G, Arroyo AG, López-Casas PP, Hidalgo M, Mulero F, Martínez-Torrecuadrada J
  Contrast Media & Molecular Imaging 2018, 8382148-.
• A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity(2018)
  Compte M, Harwood SL, Muñoz IG, Navarro R, Zonca M, Perez-Chacon G, Erce-Llamazares A, Merino N, Tapia-Galisteo A, Cuesta AM, Mikkelsen K, Caleiras E, Nuñez-Prado N, Aznar MA, Lykkemark S, Martínez-Torrecuadrada J, Melero I, Blanco FJ, Bernardino de la Serna J, Zapata JM, Sanz L, Alvarez-Vallina L
  Nat Commun 9, 4809-.
• Molecular basis of Tousled-Like Kinase 2 activation(2018)
  Mortuza GB, Hermida D, Pedersen AK, Segura-Bayona S, López-Méndez B, Redondo P, Rüther P, Pozdnyakova I, Garrote AM, Muñoz IG, Villamor-Payà M, Jauset C, Olsen JV, Stracker TH, Montoya G
  Nat Commun 9, 25-35.
• Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.(2017)
  Olmeda D, Cerezo-Wallis D, Riveiro-Falkenbach E, Pennacchi PC, Contreras-Alcalde M, Ibarz N, Cifdaloz M, Catena X, Calvo TG, Cañón E, Alonso-Curbelo D, Suarez J, Osterloh L, Graña O, Mulero F, Megías D, Cañamero M, Martínez-Torrecuadrada JL, Mondal C, Di Martino J, Lora D, Martinez-Corral I, Bravo-Cordero JJ, Muñoz J, Puig S, Ortiz-Romero P, Rodriguez-Peralto JL, Ortega S, Soengas MS
  Nature 546, 676-680.
• Modulation of telomere protection by the PI3K/AKT pathway.(2017)
  Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, García AB, Martínez -Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA
  Nat Commun 8, 1278-.
• Quorum sensing network in clinical strains of A. baumannii: AidA is a new quorum quenching enzyme.(2017)
  López M, Mayer C, Fernández-García L, Blasco L, Muras A, Ruiz FM, Bou G, Otero A, Tomás M; GEIH-GEMARA (SEIMC)
  PLoS ONE 12, e0174454-.
• A mechanism for cancer-associated inactivation of NQO1 due to P187S and its reactivation by the consensus mutation H80R.(2017)
  Muñoz IG, Morel B, Medina-Carmona E, Pey AL
  FEBS Lett 591, 2826-2835.
• Receptor-based virtual screening and biological characterization of human apurinic/apyrimidinic endonuclease (Ape1) inhibitors.(2017)
  Ruiz FM, Francis SM, Tintoré M, Ferreira R, Gil-Redondo R, Morreale A, Ortiz ÁR, Eritja R, Fàbrega C.
  ChemMedChem 7, 2168-2178.
• Display of the albumin binding domain in the envelope improves lentiviral vector bioavailability.(2017)
  Rodriguez A, Garaulet G, Lazcano JJ, Alarcón H, de Frutos S, Martínez-Torrecuadrada JL
  Hum Gene Ther Methods 28, 340-351.
• Molecular Architecture of Full Length TRF1 Favors its Interaction with DNA.(2016)
  Boskovic J, Martinez-Gago J, Mendez-Pertuz M, Buscato A, Martinez-Torrecuadrada JL, Blasco MA
  J Biol Chem 291, 21829-21835.
• Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas.(2016)
  de Lucas AG, Schuhmacher AJ, Oteo M, Romero E, Cámara JA, de Martino A, Arroyo AG, Morcillo MÁ, Squatrito M, Martinez-Torrecuadrada JL, Mulero F
  PLoS ONE 11, e0158634-.
• EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells.(2016)
  Krusche B, Ottone C, Clements MP, Johnstone ER, Goetsch K, Lieven H, Mota SG, Singh P, Khadayate S, Ashraf A, Davies T, Pollard SM, De Paola V, Roncaroli F, Martinez-Torrecuadrada J, Bertone P, Parrinello S
  Elife pii, e14845-.
• Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome.(2016)
  Pucheta-Martinez E, D'Amelio N, Lelli M, Martinez-Torrecuadrada JL, Sudol M, Saladino G, Gervasio FL
  Sci Rep 6, 30293-.
• An Allosteric Cross-Talk Between the Activation Loop and the ATP Binding Site Regulates the Activation of Src Kinase.(2016)
  Pucheta-Martínez E, Saladino G, Morando MA, Martinez-Torrecuadrada J, Lelli M, Sutto L, D'Amelio N, Gervasio FL
  Sci Rep 6, 24235-.
• Experimental and computational evidence on conformational fluctuations as a source of catalytic defects in genetic diseases.(2016)
  Fuchs JE, Muñoz IG, Timson DJ, Pey AL
  RSC ADVANCES 6, 58604-58612.
• Structural and dynamics studies of human phenylalanine hydroxilase, a highly regulated allosteric enzime.(2016)
  Flydal MI, Alcorlo M, Skjaerven S, Muñoz IG, Teigen K, Hermoso JA, Martinez A
  Acta Crystallogr A 72, S239-.
• Galectin-related protein: An integral member of the network of chicken galectins 1. From strong sequence conservation of the gene confined to vertebrates to biochemical characteristics of the chicken protein and its crystal structure.(2016)
  García Caballero G, Flores-Ibarra A, Michalak M, Khasbiullina N, Bovin NV, André S, Manning JC, Vértesy S, Ruiz FM, Kaltner H, Kopitz J, Romero A, Gabius HJ
  Biochim Biophys Acta 1860, 2285-2297.
• The structure of VgrG1 from Pseudomonas aeruginosa, the needle tip of the bacterial type VI secretion system.(2016)
  Spínola-Amilibia M, Davó-Siguero I, Ruiz FM, Santillana E, Medrano FJ, Romero A.
  Acta Crystallogr D Struct Biol 72, 22-33.
• NOTCH pathway inactivation promotes bladder cancer progression.(2015)
  Maraver A, Fernandez-Marcos PJ, Cash TP, Mendez-Pertuz M, Dueñas M, Maietta P, Martinelli P, Muñoz-Martin M, Martínez-Fernández M, Cañamero M, Roncador G, Martinez-Torrecuadrada JL, Grivas D, de la Pompa JL, Valencia A, Paramio JM, Real FX, Serrano M
  J Clin Invest 125, 824-830.
• CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma.(2015)
  Martín-Moreno AM, Roncador G, Maestre L, Mata E, Jiménez S, Martínez-Torrecuadrada JL, Reyes-García AI, Rubio C, Tomás JF, Estévez M, Pulford K, Piris MA, García JF.
  PLoS ONE 10, e0125203-.
• Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.(2015)
  Wu W, Xu C, Ling X, Fan C, Buckley BP, Chernov MV, Ellis L, Li F, Muñoz IG, Wang X
  Cell Death Dis 6, e2035-.
• Towards a Molecular Understanding of the Link Between Imatinib Resistance and Kinase Conformational Dynamics.(2015)
  Lovera S, Morando M, Pucheta-Martinez E, Martinez-Torrecuadrada JL, Saladino G, Gervasio FL
  PLoS Comput Biol (in press).
• Crystal Structure of Hcp from Acinetobacter baumannii: A Component of the Type VI Secretion System(2015)
  Ruiz FM, Santillana E, Spínola-Amilibia M, Torreira E, Culebras E, Romero A
  PLoS ONE 10, e0129691-.
• Preliminary X-ray crystallographic analysis of an engineered variant of human chimera-type galectin-3 with a shortened N-terminal domain(2015)
  Flores-Ibarra A, Ruiz FM, Vértesy S, André S, Gabius HJ, Romero A.
  Acta Crystallogr Sect F Struct Biol Cryst Commun 71, 184-188.
• Combining Crystallography and Hydrogen-Deuterium Exchange to Study Galectin-Ligand Complexes.(2015)
  Ruiz FM, Gilles U, Lindner I, André S, Romero A, Reusch D, Gabius HJ.
  Chemistry 21, 13558-13568.
• Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae.(2014)
  Bartual SG, Straume D, Stamsås GA, Muñoz IG, Alfonso C, Martínez-Ripoll M, Håvarstein LS, Hermoso JA
  Nat Communications 8, 3842-.
• Solving the RNA polymerase I structural puzzle.(2014)
  Moreno-Morcillo M, Taylor NM, Gruene T, Legrand P, Rashid UJ, Ruiz FM, Steuerwald U, Müller CW, Fernández-Tornero C.
  Acta Crystallogr D 70, 2570-2582.
• The C-terminal SH3 domain contributes to the intramolecular inhibition of Vav family proteins.(2014)
  Barreira M, Fabbiano S, Couceiro JR, Torreira E, Martínez-Torrecuadrada JL, Montoya G, Llorca O, Bustelo XR
  Sci Signal 7, ra35-.
• Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.(2014)
  Ruiz FM, Scholz BA, Buzamet E, Kopitz J, André S, Menéndez M, Romero A, Solís D, Gabius HJ
  FEBS J 281, 1446-1464.
• Purification, crystallization and preliminary X-ray diffraction analysis on the kinase domain of human Tousled Like Kinase 2 .(2014)
  Garrote AM, Redondo P, Montoya G, Muñoz IG
  Acta Crystallogr Sect F Struct Biol Cryst Commun 70, 354-357.
• SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: characterization of its expression in major hematolymphoid neoplasms.(2013)
  Montes-Moreno S, Ramos-Medina R, Martínez-López A, Barrionuevo Cornejo C, Parra Cubillos A, Quintana-Truyenque S, Rodriguez Pinilla SM, Pajares R, Sanchez-Verde L, Martinez-Torrecuadrada J, Roncador G, Piris MA
  Blood 121, 643-647.
• BCL7A protein expression in normal and malignant lymphoid tissues.(2013)
  Ramos-Medina R, Montes-Moreno S, Maestre L, Cañamero M, Rodríguez-Pinilla M, Martínez-Torrecuadrada JL, Piris MA, Majid A, Dyer MJ, Pulford K, Roncador G
  Br J Haematol 160, 106-109.
• Crystal structure of the 14-subunit RNA polymerase I.(2013)
  Fernández-Tornero C, Moreno-Morcillo M, Rashid UJ, Taylor NM, Ruiz FM, Gruene T, Legrand P, Steuerwald U, Müller CW.
  Nature 502, 644-649.
• Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies.(2013)
  Sánchez-Martín D, Martínez-Torrecuadrada J, Teesalu T, Sugahara KN, Alvarez-Cienfuegos A, Ximénez-Embún P, Fernández-Periáñez R, Martín MT, Molina-Privado I, Ruppen-Cañás I, Blanco-Toribio A, Cañamero M, Cuesta AM, Compte M, Kremer L, Bellas C, Alonso-Camino V, Guijarro-Muñoz I, Sanz L, Ruoslahti E, Alvarez-Vallina L
  Proc Natl Acad Sci USA 110, 13791-13796.
• Fine-tuning of prototype chicken galectins: structure of CG-2 and structure-activity correlations.(2013)
  Ruiz FM, Fernández IS, López-Merino L, Lagartera L, Kaltner H, Menéndez M, André S, Solís D, Gabius HJ, Romero A
  Acta Crystallogr D 69, 1665-1676.