4 years ago

Prion protein {beta}2-{alpha}2 loop conformational landscape [Biophysics and Computational Biology]

Prion protein {beta}2-{alpha}2 loop conformational landscape [Biophysics and Computational Biology]
Alessandro Barducci, Enrico Caldarulo, Michele Parrinello, Kurt Wuthrich

In transmissible spongiform encephalopathies (TSEs), which are lethal neurodegenerative diseases that affect humans and a wide range of other mammalian species, the normal “cellular” prion protein (PrPCPrPC) is transformed into amyloid aggregates representing the “scrapie form” of the protein (PrPScPrPSc). Continued research on this system is of keen interest, since new information on the physiological function of PrPCPrPC in healthy organisms is emerging, as well as new data on the mechanism of the transformation of PrPCPrPC to PrPScPrPSc. In this paper we used two different approaches: a combination of the well-tempered ensemble (WTE) and parallel tempering (PT) schemes and metadynamics (MetaD) to characterize the conformational free-energy surface of PrPCPrPC. The focus of the data analysis was on an 11-residue polypeptide segment in mouse PrPCPrPC(121–231) that includes the ββ2–αα2 loop of residues 167–170, for which a correlation between structure and susceptibility to prion disease has previously been described. This study includes wild-type mouse PrPCPrPC and a variant with the single-residue replacement Y169A. The resulting detailed conformational landscapes complement in an integrative manner the available experimental data on PrPCPrPC, providing quantitative insights into the nature of the structural transition-related function of the ββ2–αα2 loop.

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.