Structural insights into the vault ribonucleoprotein particle

• Autores: Arnau Casañas
• Directores de la Tesis: Núria Verdaguer Massana (dir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2011
• Idioma: español
• Tribunal Calificador de la Tesis: Francesc Xavier Gomis-Rüth (presid.), José Francisco Rodríguez Aguirre (secret.), Félix Rey Sayago (voc.)
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• Resumen

  • The thesis Structural Insights into the Vault particle describes the 3-D structural resolution by X-ray crystallography of the N-terminus domain of the major Vault protein and of the whole 13 megaDa Vault ribonucleoprotein particle. The combination of these structures gives a very precise picture of the interactions governing Vault association and allows the proposal of a hypothetical mechanism of Vault opening. This work also improves the overall refinement of this particle using deformable elastic network (DEN) protocols and maintaining the strict non-crystallographic symmetry of this particle. This refinement reveals a significant compression of the R1-7 structure when it is in a Vault environment. This fact could have important implications in Vault opening dynamics. The generation of recombinant Vaults and specific mutants allowed the confirmation of the previously described Vault opening hypothesis. The possibility of generating Vaults with other symmetries and sizes was also tested. This structural information represents an important step towards improving the characteristics of recombinant Vaults for drug delivery.