Viral Molecular Machines Lab



José R. Castón

Group Leader



Research summary

Our studies address to elucidate structure-function relationships of viral macromolecular complexes, also known as viral nanomachines, which control many fundamental processes in virus life cycle. For that, we have incorporated state-of-the-art approaches to obtaining near-atomic resolution structure directly from electron microscope images..



Mertens J, Casado S, Mata CP, Hernando-Pérez M, de Pablo PJ, Carrascosa JL, Castón JR. A protein with simultaneous capsid scaffolding and dsRNA-binding activities enhances the birnavirus capsid mechanical stability. Sci. Rep. 2015; 5: 13485

Llauró A, Luque D, Edwards E, Trus BL, Avera J, Reguera D, Douglas T, de Pablo PJ, Castón JR (2016). Cargo-shell and cargo-cargo couplings govern the mechanics of artificially-loaded virus-derived cages. Nanoscale 2016; 8: 8328-9336

Luque D, Mata CP, González-Camacho F, González JM, Gómez-Blanco J, Alfonso C, Rivas G, Havens WM, Kanematsu S, Suzuki N, Ghabrial SA, Trus BL, Castón JR. Heterodimers as the structural unit of the T=1 capsid of the fungal double-stranded RNA Rosellinia necatrix quadrivirus 1. J Virol. 2016;90:11220-11230.

Mata CP, Luque D, Gómez-Blanco J, Rodríguez JM, González JM, Suzuki N, Ghabrial SA, Carrascosa JL, Trus BL, Castón J. Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses. PLoS Pathog. 2017;13(12):e1006755.

Putri RM, Allende-Ballestero C, Luque D, Klem R, Rousou KA, Liu A, Traulsen CH, Rurup WF, Koay MST, Castón JR, Cornelissen JJLM. Structural characterization of native and modified encapsulins as nanoplatforms for in vitro catalysis and cellular uptake. ACS Nano. 2017. doi: 10.1021/acsnano.7b07669.

More publications


Fig1All live organisms assemble macromolecular nanomachines to carry out complex biological processes. These machines are proteins and nucleic acid-protein complexes that convert chemical energy into conformational changes; they are very dynamic and show conformational variability inherent to their mechanisms. Many fundamental cell biological and biochemical processes controlled by these macromolecular assemblies were discovered through the study of viruses, which alter cell functions and modulate cell behaviour.

As model systems of virus-derived molecular machines we study viral capsids, a paradigm of conformational flexibility, to analyse dynamic processes and macromolecular complexes that control fundamental processes in the virus life cycle. Three-dimensional (3D) structures of these macromolecular assemblies are crucial for advancing our understanding of key biological processes, i.e., how a molecular machine or protein complex works correctly or malfunctions.

We use a multidisciplinary approach that has led to structural analysis by 3D cryo-electron microscopy (cryo-EM) combined with atomic structures (hybrid approach). Our studies intend to establish the molecular interactions of the components in these complex assemblies, as well as the molecular basis of their functional implications. We have incorporated state-of-the-art approaches to obtain near-atomic resolution structure directly from two-dimensional micrographs. We are also using nanoscopic studies of these biomachines by single molecule manipulation techniques such as atomic force microscopy (AFM) to correlate structural features of capsomer interactions with their mechanical properties. Finally, virus-like particles can be used as nanocontainers to encapsulate different types of materials.

Our group studies several viral systems with varying levels of complexity, focused on a number of double-stranded (ds)RNA viruses such as the birnavirus infectious bursal disease virus (IBDV; an avian pathogen), infectious pancreatic necrosis virus (IPNV; a fish pathogen) and several fungal viruses such as Rosellinia necatrix quadrivirus 1 (RnQV1) and Penicillium chrysogenum virus (PcV), as well as single-stranded (ss)RNA viruses such as rabbit hemorrhagic disease virus (RHDV) and human rhinovirus (HRV-2). Some of these viruses cause serious diseases, and structural characterisation of their macromolecular assemblies will offer new approaches to altering their function, as well as possible vaccination strategies. Modified capsids offer excellent opportunities in nanotechnology and nanomedicine.





José R. Castón Principal investigator
Javier M. Rodríguez Senior investigator
Alvaro Ortega-Esteban Postdoctoral researcher
Carolina Allende Ballestero Predoctoral scientist
David Gil Cantero Predoctoral scientist  
Celia García Gutiérrez Predoctoral scientist  
María J. Rodríguez-Espinosa Master student  
Esther Martín Forero Technician


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