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J Biol Chem. 2014 Jul 18;289(29):19850-4. doi: 10.1074/jbc.R113.511329. Epub 2014 May 23.

Synthesis of high titer infectious prions with cofactor molecules.

Author information

1
From the Departments of Biochemistry and Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755 supattapone@dartmouth.edu.

Abstract

Recently, synthetic prions with a high level of specific infectivity have been produced from chemically defined components in vitro. A major insight arising from these studies is that various classes of host-encoded cofactor molecules such as phosphatidylethanolamine and RNA molecules are required to form and maintain the specific conformation of infectious prions. Synthetic mouse prions formed with phosphatidylethanolamine exhibit levels of specific infectivity ∼1 million-fold greater than "protein-only" prions (Deleault, N. R., Walsh, D. J., Piro, J. R., Wang, F., Wang, X., Ma, J., Rees, J. R., and Supattapone, S. (2012) Proc. Natl. Acad. Sci. U.S.A. 109, E1938-E1946). Moreover, cofactor molecules also appear to regulate prion strain properties by limiting the potential conformations of the prion protein (see Deleault et al. above). The production of fully infectious synthetic prions provides new opportunities to study the mechanism of prion infectivity directly by structural and biochemical methods.

KEYWORDS:

Cofactor; Infectivity; Phosphatidylethanolamine; Phospholipid; Prion; Protein Misfolding; RNA; Synthetic

PMID:
24860097
PMCID:
PMC4106305
DOI:
10.1074/jbc.R113.511329
[Indexed for MEDLINE]
Free PMC Article

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