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The Rich Chemistry of the Copper and Zinc Sites in PrPC

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Prions and Diseases

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Abstract

Research over the last two decades demonstrates clearly that the function of the cellular form of the prion protein, PrPC, is related to its ability to bind copper and zinc. Zinc (Zn2+) coordination is homogeneous and localized to the octarepeat domain, with participation of the histidine side chains. In contrast, copper uptake is complex and dependent on the oxidation state of the metal ion (Cu+ or Cu2+) and its concentration. This chapter will cover a brief history of PrPC–metal interactions leading to the current structural models, Cu2+-promoted structural features that protect against PrPC neurotoxicity, a recently recognized relationship between Cu2+ coordination and inherited prion disease arising from octarepeat inserts, assessment of PrP-copper electrochemical features, with insight into the basis of PrPC neuroprotection and transmembrane signaling, and recent findings of how copper participates in the regulation of PrPC proteolysis.

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Acknowledgments

This work was supported by NIH grant R35 GM131781. The author wishes to thank Professor F. Zhou of California State University, Los Angeles, and Ms. Amy Freiberg, UC Santa Cruz for helpful insights and editorial comments.

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Authors and Affiliations

  1. Department of Chemistry & Biochemistry, University of California Santa Cruz, Santa Cruz, CA, USA

    Glenn L. Millhauser

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  1. Glenn L. Millhauser
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Correspondence to Glenn L. Millhauser .

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Editors and Affiliations

  1. Departments of Pathology and Neurology, National Prion Disease Pathology Surveillance Center, National Center for Regenerative Medicine Case Western Reserve University, School of Medicine, Cleveland, OH, USA

    Wen-Quan Zou

  2. Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Pierluigi Gambetti

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Millhauser, G.L. (2023). The Rich Chemistry of the Copper and Zinc Sites in PrPC. In: Zou, WQ., Gambetti, P. (eds) Prions and Diseases. Springer, Cham. https://doi.org/10.1007/978-3-031-20565-1_2

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