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Hemin interactions and alterations of the subcellular localization of prion protein.

Authors
  • Lee, Kil S
  • Raymond, Lynne D
  • Schoen, Brianna
  • Raymond, Gregory J
  • Kett, Lauren
  • Moore, Roger A
  • Johnson, Lisa M
  • Taubner, Lara
  • Speare, Jonathan O
  • Onwubiko, Henry A
  • Baron, Gerald S
  • Caughey, Winslow S
  • Caughey, Byron
Type
Published Article
Journal
The Journal of biological chemistry
Publication Date
Dec 14, 2007
Volume
282
Issue
50
Pages
36525–36533
Identifiers
PMID: 17925394
Source
Medline
License
Unknown

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 microM) 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.

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