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Course Abstracts

  • Joseph D. Puglisi
  • Manolia V. Margaris
Conference paper
Part of the NATO Science for Peace and Security Series B: Physics and Biophysics book series (NAPSB)

Abstract

Prions are fatal neurodegenerative transmissible agents causing many diseases (e.g. Creutzfeldt-Jakob disease in human, spongiform encephalopathy in bovine and scrapie in sheep). The structural investigation of prions is challenging due to the protein intrinsic disorder (mostly located in the N-terminal region). We used PrP specific nanobodies derived from Camelid antibodies to determine the structure of full-length mouse PrPC (23–230) by x-ray crystallography. Initial attempts to co-crystallize full-length mouse PrPC in complex with Nb484 did not produce crystals. However, limited *in-situ* proteolysis produced plate-like crystals which diffracted to 2.7 Å resolution. Here we report the characterization at molecular level of the interaction of mouse PrPC and a nanobody (Nb484).

Our goal is to use nanobodies as a molecular tool to obtain a better understanding of the mechanism of the amyloidogenic disease formation. We also crystallized Nb484 alone and collected a complete dataset at high resolution (1.2 Å). Our experiments suggest that the nanobodies can be used as a molecular tool by helping the crystallization and by inhibiting the PrPC to PrPSc transition.

Keywords

Structural Biology Cholesterol Sulfate Protochlorophyllide Oxidoreductase Protein Intrinsic Disorder Italy Department 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Joseph D. Puglisi
    • 1
  • Manolia V. Margaris
    • 1
  1. 1.Stanford UniversityStanfordUSA

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