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]](/image/eyJ1cmkiOiJodHRwOi8vc3RhY2thZGVtaWMuaGVyb2t1YXBwLmNvbS9pbWFnZT9pbWFnZV9pZD0xNDgwNSIsImZvcm1hdCI6IndlYnAiLCJxdWFsaXR5IjoxMDAsIm5vQ2FjaGUiOnRydWV9.webp)
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 (
PrPC) is transformed into amyloid aggregates representing the “scrapie form” of the protein (
PrPSc). Continued research on this system is of keen interest, since new information on the physiological function of
PrPC in healthy organisms is emerging, as well as new data on the mechanism of the transformation of
PrPC to
PrPSc. 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
PrPC. The focus of the data analysis was on an 11-residue polypeptide segment in mouse
PrPC(121–231) that includes the
β2–
α2 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
PrPC and a variant with the single-residue replacement Y169A. The resulting detailed conformational landscapes complement in an
integrative manner the available experimental data on
PrPC, providing quantitative insights into the nature of the structural transition-related function of the
β2–
α2 loop.
Publisher URL: http://feedproxy.google.com/~r/Pnas-RssFeedOfEarlyEditionArticles/~3/UnrcGuvOUY4/1712155114.short
DOI: 10.1073/pnas.1712155114
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.
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.