Hemin interactions and alterations of the subcellular localization of prion protein

Kil S. Lee, Lynne D. Raymond, Brianna Schoen, Gregory J. Raymond, Lauren Kett, Roger A. Moore, Lisa M Johnson, Lara Taubner, Jonathan O. Speare, Henry A. Onwubiko, Gerald S. Baron, Winslow S. Caughey, Byron Caughey

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Hemin (iron protoporphyrin IX) is a crucial component of many physiological processes acting either as a prosthetic group or as an intracellular messenger. Some unnatural, synthetic porphyrins have potent anti-scrapie activity and can interact with normal prion protein (PrPC). These observations raised the possibility that hemin, as a natural porphyrin, is a physiological ligand for PrPC. Accordingly, we evaluated PrPC interactions with hemin. When hemin (3-10 μM) was added to the medium of cultured cells, clusters of PrPC formed on the cell surface, and the detergent solubility of PrPC decreased. The addition of hemin also induced PrPC internalization and turnover. The ability of hemin to bind directly to PrPC was demonstrated by hemin-agarose affinity chromatography and UV-visible spectroscopy. Multiple hemin molecules bound primarily to the N-terminal third of PrPC, with reduced binding to PrPC lacking residues 34-94. These hemin-PrPC interactions suggest that PrPC may participate in hemin homeostasis, sensing, and/or uptake and that hemin might affect PrPC functions.

Original languageEnglish (US)
Pages (from-to)36525-36533
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number50
DOIs
StatePublished - Dec 14 2007

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