Tesis doctoral de Nuria González Montalban
Recombinant proteins produced in escherichia coli tend to aggregate as intracellular deposits made of insoluble material known as inclusion bodies. Such aggregates can be observed as retractile particles by optical microscopy and as electrodense protein clusters by transmission electron microscopy, showing ovoid or spherical shapes. Inclusion bodies are normally found in the cytoplasm although can be also localized in the periplasm. Nevertheless, the classical conception of inclusion bodies as heterogeneous and disordered aggregates driven by random interactions has sharply changed in the last years. this phd thesis demonstrates that bacterial inclusion bodies are highly ordered aggregates, structured in intermolecular, antiparallel b-sheet pattern, driven by specific interactions, and retaining native-like structure and thus biological activity. All those features resemble those found in amyloid fibrils. Indeed, as it happens in amyloid aggregates, inclusion bodies exhibit toxicity in some chaperone-deficient strains and in mammalian cells lines. Furthermore, the physiological disintegration of inclusion bodies is a non-selective process although it is compatible with an in situ folding process negatively controlled by the chaperone dnak. overall, the data support the hypothesis that bacterial systems could be used to explore protein misfolding and aggregation processes by means of a fast, simple and biologically relevant experimental model
Datos académicos de la tesis doctoral «Structural biology of bacterial inclusion bodies«
- Título de la tesis: Structural biology of bacterial inclusion bodies
- Autor: Nuria González Montalban
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 14/11/2008
Dirección y tribunal
- Director de la tesis
- Antonio Villaverde Corrales
- Tribunal
- Presidente del tribunal: jordi Barbé García
- jordi xavier Feliu gil (vocal)
- ursula Rinas (vocal)
- antoni Benito mundet (vocal)