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Structural Biology Programme

Crystallography and Protein Engineering Unit

Head of Unit:  Inés Muñoz
Research highlights

This year, we worked closely with the Experimental Therapeutics Programme on several projects based on the production of proteins such as full-length human MASTL that enable new biochemical experiments. Other projects were directly focused on structural characterisation by X-ray crystallography in support of drug discovery projects, as was the case of the human proteins MASTL kinase-domain, HASPIN and CDK8/CyclinC complex in which the proteins were crystallised in the presence of compounds developed at the Medicinal Chemistry Section (FIGURE). Especially relevant was our continuous work on the production of proteins for the generation of antibodies by the Monoclonal Antibody Unit (Biotechnology Programme). During 2017, this smooth collaboration has led to the production of several cancer-involved proteins such as mouse PD1, PD-L2 and HAS1, and human IL11 and NOMO1, among others.

The Unit also undertakes several internal collaborations with other CNIO Groups. Especially noteworthy are the ones established with the Telomeres and Telomerase Group, the Gastrointestinal Cancer Clinical Research Unit, the Melanoma Group, and the Experimental Oncology Group. Additionally, the Unit maintains external collaborations with groups at the Physical Chemistry Department (University of Granada), the Environmental Biology Department (CIB-CSIC), the Department of Biomedicine (University of Bergen, Norway), the Department of Crystallography and Structural Biology (Instituto de QuimicaFisica Rocasolano, CSIC), and the Department of Molecular Engineering (Åarhus University, Denmark).

Along 2017, the Unit also sustained its own scientific projects. We continued to characterise the role of ephrinB2 in different pathologies by carrying out a further structural characterisation of the blocking single-chain antibodies, which we developed at our Unit by using a combination of X-ray crystallography and SAXS (FIGURE). We have also initiated a drug-discovery project targeting the function of the Mdm2-MdmX E3 complex, in collaboration with the Pharmacology and Therapeutics Department at the Roswell Park Cancer Institute (Buffalo, USA).