Prion’s Multiple Roles | Chemical & Engineering News
Volume 89 Issue 31 | p. 36 | Concentrates
Issue Date: August 1, 2011

Prion’s Multiple Roles

Department: Science & Technology
News Channels: JACS In C&EN
Keywords: prion, mad cow disease, protein misfolding, electrochemistry
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PrP/multiple-Cu2+ generates H2O2 and may have a signaling role.
Credit: Courtesy of Glenn Millhauser
Dual Role -- PrP/single-Cu2+ quenches copper’s inherent redox activity, but PrP/four-Cu2+ generates peroxide, a signaling compound. PrP may therefore have both a protective and a signaling role.
 
PrP/multiple-Cu2+ generates H2O2 and may have a signaling role.
Credit: Courtesy of Glenn Millhauser

A recent study hints at protective and signaling roles for prion protein (PrP). When misfolded, PrP is believed to cause mad cow disease in cattle and Creutzfeldt-Jakob disease in people—both untreatable and fatal brain diseases. But the role of endogenous PrP isn’t known. It binds copper, but why it does so is uncertain. Glenn L. Millhauser of the University of California, Santa Cruz; Feimeng Zhou of California State University, Los Angeles; and coworkers have now carried out an electrochemical study that may provide an answer. They report that binding of a single Cu2+ ion to a key PrP domain quiets copper’s inherent redox activity, but PrP binding of multiple Cu2+ ions leads to gentle and controlled generation of the cellular-signaling compound hydrogen peroxide via catalytic oxygen reduction (J. Am. Chem. Soc., DOI: 10.1021/ja2045259). The discovery suggests that PrP has a dual role: PrP/single-Cu2+ may protect against cellular damage and PrP/multiple-Cu2+ may turn on intracellular signaling. The work is “very convincing, and although the findings need further verification, they represent an entirely new and exciting way of thinking about this protein,” says metalloprotein specialist Jason M. Shearer of the University of Nevada, Reno.

 
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