Carmen San Martín
Group Leader
Research summary
We are interested in the structural and physical principles that govern assembly and stabilisation of complex viruses. As a model system we use adenovirus, a challenging specimen of interest both in basic virology and in nanobiomedicine. We approach the problem from an interdisciplinary point of view, combining biophysics, computational, structural and molecular biology techniques.
Accurate knowledge of adenovirus structure and biology is fundamental to both the discovery of anti-adenovirus drugs and the design of new, efficient adenoviral therapeutic tools.
Publications
Marabini R, Condezo GN, Krupovi M., Menéndez-Conejero R, Gómez-Blanco J, and San Martín C. Near Atomic Structure of an Atadenovirus Reveals a Conserved Capsid-Binding Motif and Intergenera Variations in Cementing Proteins. Sci Adv 2021, 7 (14), doi: 10.1126/sciadv.abe6008.
Pérez-Illana M, Martínez M, Condezo GN, Hernando-Pérez M, Mangroo C, Brown M, Marabini R. and San Martín C. Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural variations among human adenoviruses. Sci Adv 2021; 7 (9), doi: 10.1126/sciadv.abd9421.
Hernando-Pérez, M, Martín-González, N, Pérez-Illana, M, Suomalainen, M, Condezo, GN, Ostapchuk, P, Gallardo, J, Menéndez, M, Greber, UF, Hearing, P, de Pablo, PJ and San Martín, C. Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry. Proceedings of the National Academy of Sciences 2020; 201920896. doi:10.1073/pnas.1920896117.
Martín-González N, Hernando-Pérez M, Condezo GN, Pérez-Illana M, Šiber A, Reguera D, Ostapchuk P, Hearing P, San Martín C, and de Pablo PJ. Adenovirus major core protein condenses DNA in clusters and bundles, modulating genome release and capsid internal pressure. Nucleic Acids Res 2019; 47, 9231-9242. doi:10.1093/nar/gkz687
San Martín C, and van Raaij MJ. The so far farthest reaches of the double jelly roll capsid protein fold. Virology Journal 2018; 15, 181. doi:10.1186/s12985-018-1097-1.
Condezo GN, San Martín C. Localization of adenovirus morphogenesis players, together with visualization of assembly intermediates and failed products, favor a model where assembly and packaging occur concurrently at the periphery of the replication center. PLoS Pathog 2017; 13(4): e1006320.
Adenoviruses (AdVs) are pathogens with particular clinical relevance in the immunocompromised population. They are widely used as vectors for gene therapy, vaccination and oncolysis. AdVs have one of the most complex icosahedral, non-enveloped capsids known. Their genome, a dsDNA molecule, is bound to large amounts of positively charged proteins that help condense it and form the core, which is confined within an icosahedral capsid composed of multiple copies of seven viral proteins. The final stage of adenovirus morphogenesis consists of proteolytic processing of several capsid and core proteins. The immature virus, which contains all precursor proteins, is not infectious due to an uncoating defect. Although more than 200 types of AdV have been isolated from a variety of vertebrates, most current knowledge of their biology is derived from a few human AdV.
Our current research lines focus on the less understood aspects of AdV assembly, such as: how the viral genome is packaged into the capsid; how does maturation occur; what are the key elements modulating virion stability and mechanical properties; what is the organization of the non-icosahedral virion components. Finally, we explore the structure and assembly of AdVs belonging to scarcely characterized species and genera.