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 whose main goal is to supply the requests of the research groups within the CNIO, as well as external groups, by providing on-demand services at different levels. The Unit covers all the services that range from the coding sequence cloning to the resolution of the 3D structure, whilst always focusing on helping the research groups in reaching a broader characterisation of their proteins of interest. These services span the production of proteins for different types of biochemical/biophysical assays, monoclonal antibody production, and macromolecular structural determination at low resolution by small-angle X-ray scattering (SAXS) or at high resolution by X-ray crystallography. The latter includes protein co-crystallisation − a method that we routinely combine with the quantification of the protein thermal stability (thermofluor assay) − in the presence of inhibitors during the structure guided drug discovery process.

Publications

• Garaulet G, Pérez-Chacon G, Alarcón H, Alfranca A, Mulero F, Martínez-Torrecuadrada J, Zapata JM, Rodríguez A (2019). Intratumoral expression using a NFkB-based promoter enhances IL12 antitumor efficacy. Cancer Gene Ther (in press).
• 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 (2019). Pancreatic Tumor Microenvironment Modulation by EphB4-ephrinB2 Inhibition and Radiation Combination. Clin Cancer Res (in press).
• 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 (2018). Exome Sequencing of Plasma DNA Portrays the Mutation Landscape of Colorectal Cancer and Discovers Mutated VEGFR2 Receptors as Modulators of Antiangiogenic Therapies. Clin Cancer Res 24, 3550-3559.
• 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 (2018). MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management. Contrast Media & Molecular Imaging 2018, 8382148.
• 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 (2018). A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity. Nat Commun 9, 4809.
• 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 (2018). Molecular basis of Tousled-Like Kinase 2 activation. Nat Commun 9, 25-35.
• 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 (2017). Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.. Nature 546, 676-680.
• 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 (2017). Modulation of telomere protection by the PI3K/AKT pathway.. Nat Commun 8, 1278.
• López M, Mayer C, Fernández-García L, Blasco L, Muras A, Ruiz FM, Bou G, Otero A, Tomás M; GEIH-GEMARA (SEIMC) (2017). Quorum sensing network in clinical strains of A. baumannii: AidA is a new quorum quenching enzyme.. PLoS ONE 12, e0174454.
• Muñoz IG, Morel B, Medina-Carmona E, Pey AL (2017). A mechanism for cancer-associated inactivation of NQO1 due to P187S and its reactivation by the consensus mutation H80R.. FEBS Lett 591, 2826-2835.
• Ruiz FM, Francis SM, Tintoré M, Ferreira R, Gil-Redondo R, Morreale A, Ortiz ÁR, Eritja R, Fàbrega C. (2017). Receptor-based virtual screening and biological characterization of human apurinic/apyrimidinic endonuclease (Ape1) inhibitors.. ChemMedChem 7, 2168-2178.
• Rodriguez A, Garaulet G, Lazcano JJ, Alarcón H, de Frutos S, Martínez-Torrecuadrada JL (2017). Display of the albumin binding domain in the envelope improves lentiviral vector bioavailability.. Hum Gene Ther Methods 28, 340-351.
• Boskovic J, Martinez-Gago J, Mendez-Pertuz M, Buscato A, Martinez-Torrecuadrada JL, Blasco MA (2016). Molecular Architecture of Full Length TRF1 Favors its Interaction with DNA.. J Biol Chem 291, 21829-21835.
• 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 (2016). Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas.. PLoS ONE 11, e0158634.
• 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 (2016). EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells.. Elife pii, e14845.
• Pucheta-Martinez E, D'Amelio N, Lelli M, Martinez-Torrecuadrada JL, Sudol M, Saladino G, Gervasio FL (2016). Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome.. Sci Rep 6, 30293.
• Pucheta-Martínez E, Saladino G, Morando MA, Martinez-Torrecuadrada J, Lelli M, Sutto L, D'Amelio N, Gervasio FL (2016). An Allosteric Cross-Talk Between the Activation Loop and the ATP Binding Site Regulates the Activation of Src Kinase.. Sci Rep 6, 24235.
• Fuchs JE, Muñoz IG, Timson DJ, Pey AL (2016). Experimental and computational evidence on conformational fluctuations as a source of catalytic defects in genetic diseases.. RSC ADVANCES 6, 58604-58612.
• Flydal MI, Alcorlo M, Skjaerven S, Muñoz IG, Teigen K, Hermoso JA, Martinez A (2016). Structural and dynamics studies of human phenylalanine hydroxilase, a highly regulated allosteric enzime.. Acta Crystallogr A 72, S239.
• 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 (2016). 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.. Biochim Biophys Acta 1860, 2285-2297.
• Spínola-Amilibia M, Davó-Siguero I, Ruiz FM, Santillana E, Medrano FJ, Romero A. (2016). The structure of VgrG1 from Pseudomonas aeruginosa, the needle tip of the bacterial type VI secretion system.. Acta Crystallogr D Struct Biol 72, 22-33.
• 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 (2015). NOTCH pathway inactivation promotes bladder cancer progression.. J Clin Invest 125, 824-830.
• 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. (2015). CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma.. PLoS ONE 10, e0125203.
• Wu W, Xu C, Ling X, Fan C, Buckley BP, Chernov MV, Ellis L, Li F, Muñoz IG, Wang X (2015). Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.. Cell Death Dis 6, e2035.
• Lovera S, Morando M, Pucheta-Martinez E, Martinez-Torrecuadrada JL, Saladino G, Gervasio FL (2015). Towards a Molecular Understanding of the Link Between Imatinib Resistance and Kinase Conformational Dynamics.. PLoS Comput Biol (in press).
• Ruiz FM, Santillana E, Spínola-Amilibia M, Torreira E, Culebras E, Romero A (2015). Crystal Structure of Hcp from Acinetobacter baumannii: A Component of the Type VI Secretion System. PLoS ONE 10, e0129691.
• Flores-Ibarra A, Ruiz FM, Vértesy S, André S, Gabius HJ, Romero A. (2015). Preliminary X-ray crystallographic analysis of an engineered variant of human chimera-type galectin-3 with a shortened N-terminal domain. Acta Crystallogr Sect F Struct Biol Cryst Commun 71, 184-188.
• Ruiz FM, Gilles U, Lindner I, André S, Romero A, Reusch D, Gabius HJ. (2015). Combining Crystallography and Hydrogen-Deuterium Exchange to Study Galectin-Ligand Complexes.. Chemistry 21, 13558-13568.
• Bartual SG, Straume D, Stamsås GA, Muñoz IG, Alfonso C, Martínez-Ripoll M, Håvarstein LS, Hermoso JA (2014). Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae.. Nat Communications 8, 3842.
• Moreno-Morcillo M, Taylor NM, Gruene T, Legrand P, Rashid UJ, Ruiz FM, Steuerwald U, Müller CW, Fernández-Tornero C. (2014). Solving the RNA polymerase I structural puzzle.. Acta Crystallogr D 70, 2570-2582.
• Barreira M, Fabbiano S, Couceiro JR, Torreira E, Martínez-Torrecuadrada JL, Montoya G, Llorca O, Bustelo XR (2014). The C-terminal SH3 domain contributes to the intramolecular inhibition of Vav family proteins.. Sci Signal 7, ra35.
• Ruiz FM, Scholz BA, Buzamet E, Kopitz J, André S, Menéndez M, Romero A, Solís D, Gabius HJ (2014). Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.. FEBS J 281, 1446-1464.
• Garrote AM, Redondo P, Montoya G, Muñoz IG (2014). Purification, crystallization and preliminary X-ray diffraction analysis on the kinase domain of human Tousled Like Kinase 2 .. Acta Crystallogr Sect F Struct Biol Cryst Commun 70, 354-357.
• 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 (2013). SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: characterization of its expression in major hematolymphoid neoplasms.. Blood 121, 643-647.
• 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 (2013). BCL7A protein expression in normal and malignant lymphoid tissues.. Br J Haematol 160, 106-109.
• Fernández-Tornero C, Moreno-Morcillo M, Rashid UJ, Taylor NM, Ruiz FM, Gruene T, Legrand P, Steuerwald U, Müller CW. (2013). Crystal structure of the 14-subunit RNA polymerase I.. Nature 502, 644-649.
• 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 (2013). Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies.. Proc Natl Acad Sci USA 110, 13791-13796.
• Ruiz FM, Fernández IS, López-Merino L, Lagartera L, Kaltner H, Menéndez M, André S, Solís D, Gabius HJ, Romero A (2013). Fine-tuning of prototype chicken galectins: structure of CG-2 and structure-activity correlations.. Acta Crystallogr D 69, 1665-1676.