Research director, professor
Protein Structure and Function Program
Blegdamsvej 3, 2200 København N, Bygning 6, Building: 06-1-30
Professor Guillermo Montoya is Research Director and Group Leader at the Protein Structure and Function program at Novo Nordisk Foundation Center for Protein Research (CPR) at University of Copenhagen.
Guillermo Montoya’s research aims to understand basic cellular mechanisms at the atomic level, and he firmly believes that the detailed unravelling of these mechanisms will be essential for future biomedical research.
The approach of the Montoya Group is to use advanced methodology, combining X-ray crystallography and cryo-electron microscopy with cell biology to study the structure and function of macromolecules involved in cell cycle progression, genome integrity and its manipulation.
Montoya solved the first crystal structure of the 1 MDa TRiC/CCT chaperonin in complex with tubulin, shedding light on the folding mechanism that is essential for cell cycle progression and chromosome segregation. His group has recently provided molecular evidence of how key guardians of genome integrity such as the kinase TLK2 or the XMAP215 microtubule polymerase work to protect the genome and provide faithful cell division.
Montoya is also systematically pursuing the structure-function analysis of endonucleases, which are of great interest because of their applications in genome editing. His seminal work in homing endonucleases has shown that these proteins were amenable of redesign in order to target mutations in human monogenic diseases.
His studies elucidating the structure of CRISPR-Cas12a interference ribonucleoprotein have unveiled the mechanism of recognition, unzipping and catalytic activation in order to cleavage target DNA. This finding has opened new avenues in genome modification for biomedicine and biotechnology.
- Molecular activation mechanisms of oligomeric kinases involved in genome integrity
- Protein complexes involved in telomere maintenance and integrity
- Conformational activation of CRISPR-Cas12a catalysis and its redesign to generate new molecular scissors
- Mechanisms for foreign RNA and DNA degradation by macromolecular complexes
Recent Key Publications
Stella S, Alcón P, Montoya G. Structural Biology of RNA-guided Endonucleases: The Swiss-Army knives of Genome Editing. NatureStructural&MolecularBiology (2017) Nov;24(11):882-892.
Stella S, Alcón P, Montoya G. Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage. Nature (2017) 546(7659):559-563.
Molina R, Stella S, Redondo P, Gomez H, Marcaida MJ, Orozco M, Prieto J, Montoya G. Visualizing phosphodiester-bond hydrolysis by an endonuclease. Nature Structural & Molecular Biology (2015) Jan;22(1):65-72. doi: 10.1038/nsmb.2932.
Mortuza GB, Cavazza T, Garcia-Mayoral MF, Hermida D, Peset I, Pedrero JG, Merino N, Blanco FJ, Lyngsø J, Bruix M, Pedersen JS, Vernos I, Montoya G. XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation. Nature Communications (2014) Sep 29; 5:5072. doi: 10.1038/ncomms6072.
Muñoz, I.G., Yébenes, H., Zhou M., Mesa, P. Serna, M. Bragado-Nilsson, Beloso, A., E. de Carcer G., Malumbres M., Robinson C.V., Valpuesta, J.M. & Montoya G. Crystal structure of the mammalian cytosolic chaperonin CCT in complex with tubulin Nature Structural & Molecular Biology (2011) Jan;18(1):14-9.
Molecular basis of recognition and cleavage of the human Xeroderma pigmentosum group C gene by engineered homing endonuclease heterodimers. P. Redondo, J. Prieto, I. Muñoz, A. Alibés, F. Strichter, L. Serrano, S., P. Duchateau, F. Paques, F. Blanco & Montoya G. Nature. (2008) Nov 6;456(7218):107-11