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Allosteric function and dysfunction of the prion protein

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Abstract

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases associated with progressive oligo- and multimerization of the prion protein (PrPC), its conformational conversion, aggregation and precipitation. We recently proposed that PrPC serves as a cell surface scaffold protein for a variety of signaling modules, the effects of which translate into wide-range functional consequences. Here we review evidence for allosteric functions of PrPC, which constitute a common property of scaffold proteins. The available data suggest that allosteric effects among PrPC and its partners are involved in the assembly of multi-component signaling modules at the cell surface, impose upon both physiological and pathological conformational responses of PrPC, and that allosteric dysfunction of PrPC has the potential to entail progressive signal corruption. These properties may be germane both to physiological roles of PrPC, as well as to the pathogenesis of the TSEs and other degenerative/non-communicable diseases.

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Acknowledgments

The authors' work is supported by grants from CNPq, FAPERJ, and the National Institute of Structural Biology and Bioimaging (INBEB-MCT).

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  1. Instituto de Biofísica Carlos Chagas Filho, UFRJ, CCS, bloco G, Cidade Universitária, Rio de Janeiro, 21941-902, Brazil

    Rafael Linden

  2. Faculdade de Farmácia, UFRJ, Rio de Janeiro, 21941-902, Brazil

    Yraima Cordeiro & Luis Mauricio T. R. Lima

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  1. Rafael Linden
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Correspondence to Rafael Linden.

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Linden, R., Cordeiro, Y. & Lima, L.M.T.R. Allosteric function and dysfunction of the prion protein. Cell. Mol. Life Sci. 69, 1105–1124 (2012). https://doi.org/10.1007/s00018-011-0847-7

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