Unidad de Cristalografía e Ingeniería de Proteínas

Inés Muñoz Jefe de Unidad
T +34 917328000 (Ext 3020)
imunoz@cnio.es

Investigadores

Jorge Luís Martínez

Becarios Post-doctorales

Virginia Sandonís

Técnicos de Laboratorio

Aida Contreras
Diana Martín
Álvaro Otero
Pilar Redondo

The Crystallography and Protein Engineering Unit (XTPEUnit) is a core facility that provides on-demand services at different levels, from protein cloning to the determination of its 3D structure, with the purpose to fulfil the demands of our users and to comprehend how their protein targets work. Thus, we produce proteins for different types of biochemical/biophysical/in vitro/in vivo assays, for monoclonal antibody generation, and we also offer macromolecular structural determination at low resolution by small-angle X-ray scattering (SAXS) or at atomic resolution by X-ray crystallography. The latter includes protein co-crystallisation in the presence of inhibitors or small fragments − a method that we routinely combine in parallel with the quantification of protein thermal stability (thermofluor assay) − during the guided drug discovery process.

Publicaciones

Martínez-González S, García AB, Albarrán MI, Cebriá A, Amezquita-Alves A, García-Campos FJ, Martínez-Gago J, Martínez-Torrecuadrada J, Muñoz I, Blanco-Aparicio C, Pastor J (2020). Pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives as CDK8 inhibitors.. Eur J Med Chem 201, 112443. Publicación CNIO.
Frye M, Stritt S, Ortsäter H, Hernandez Vasquez M, Kaakinen M, Vicente A, Wiseman J, Eklund L, Martínez-Torrecuadrada JL, Vestweber D, Mäkinen T (2020). EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity. Elife 8, e57732. Publicación CNIO.
de Salas F, Cañadas R, Santiago G, Virseda-Jerez A, Vind J, Gentili P, Martínez AT, Guallar V, Muñoz IG, Camarero S (2019). Structural and biochemical insights into an engineered high-redox potential laccase overproduced in Aspergillus.. Int J Biol Macromol 141, 855-866. Publicación CNIO.
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 26, 216-233. Publicación CNIO.
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 25, 3352-3365. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO. Open Access
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación en otras instituciones.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación en otras instituciones.
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. Publicación en otras instituciones.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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). Publicación CNIO.
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. Publicación en otras instituciones.
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. Publicación en otras instituciones.
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. Publicación en otras instituciones.
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. Publicación CNIO.