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Prion protein—Semisynthetic prion protein (PrP) variants with posttranslational modifications
Author(s) -
Hackl Stefanie,
Becker Christian F.W.
Publication year - 2019
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3216
Subject(s) - semisynthesis , glycosylation , scrapie , prion protein , chemistry , proteolysis , in vitro , microbiology and biotechnology , biochemistry , native chemical ligation , peptide , computational biology , biology , chemical synthesis , medicine , disease , pathology , enzyme
Deciphering the pathophysiologic events in prion diseases is challenging, and the role of posttranslational modifications (PTMs) such as glypidation and glycosylation remains elusive due to the lack of homogeneous protein preparations. So far, experimental studies have been limited in directly analyzing the earliest events of the conformational change of cellular prion protein (PrP C ) into scrapie prion protein (PrP Sc ) that further propagates PrP C misfolding and aggregation at the cellular membrane, the initial site of prion infection, and PrP misfolding, by a lack of suitably modified PrP variants. PTMs of PrP, especially attachment of the glycosylphosphatidylinositol (GPI) anchor, have been shown to be crucially involved in the PrP Sc formation. To this end, semisynthesis offers a unique possibility to understand PrP behavior in vitro and in vivo as it provides access to defined site‐selectively modified PrP variants. This approach relies on the production and chemoselective linkage of peptide segments, amenable to chemical modifications, with recombinantly produced protein segments. In this article, advances in understanding PrP conversion using semisynthesis as a tool to obtain homogeneous posttranslationally modified PrP will be discussed.