Prion proteins : the différance in the fold

Abstract : Protein (and nucleic acid) folding can be viewed as biological morphogenesis at its most elementary stage. Protein function is strictly related to folding, thus most if not all biological phenomena are rooted in this elementary folding process. Protein folding can be described as « a form of adaption to growth processes » as during protein synthesis, while the polypeptide grows and emerges from the exit tunnel of the ribosome, it gradually acquires physiochemical properties eventually triggering its folding, into a unique and strictly defined native structure. Since Anfinsen, we posit that all the information required for the acquisition of the native fold of the protein is encoded in its primary sequence hence in the DNA of the corresponding gene. Yet, the relation of the code to the fold is dauntingly complex and far from being fully understood, and the problem of protein folding is arguably still one of the central unresolved questions in modern biology. This relation is particularly ambiguous in the case of prions, because such proteins can display alternate, non-prion and prion folds. The prion fold is acquired cooperatively as an emergent property and is then transmitted to the non-prion form by templating. We propose to treat the relation of code to fold in the specific case of prion proteins, focusing on functional fungal prions. For disease-associated prions (which attracted public attention during the mad cow disease crisis) acquisition and infectious transmission of the fold is a mishap. In contrast for such fungal prions, it is a natural function. While those are still missing in the case of mammalian disease-associated prions, high resolution structures of fungal prions are currently available. We will show that such folds are genetic information, determining a phenotype, and transmitted from cell to cell or from generation to generation. We will discuss, using this example, the different levels of coding embedded in the DNA sequence. We will attempt to use the Derridian motif of the difference to frame the description of this elementary folding process. Indeed, in this system one experiences a temporal and spatial separation in the coding of matter and coding of the fold. In the non-prion and prion state these proteins differ in fold but are identical in chemical content and, acquisition of the fold (which represents the functional thus meaningful state) is differed and not synchronic with synthesis (acquisition of materiality). We hope with this example to participate in the questioning of the determinism in folding processes and the relation of folds to symbolic (coding) systems.
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https://halshs.archives-ouvertes.fr/halshs-01445907
Contributor : Sonia Dheur <>
Submitted on : Wednesday, January 25, 2017 - 2:24:08 PM
Last modification on : Tuesday, July 9, 2019 - 10:05:01 AM

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Sonia Dheur, Sven J Saupe. Prion proteins : the différance in the fold. The Fold (EnsAD/ESPCI), Peter Fratzl (MPI of Colloids and Interfaces, Potsdam) Michael Friedman (Humboldt University, Berlin) Benoît Roman (ESPCI, Paris) Dominique Peysson (EnsAD, Paris), Sep 2016, Paris, France. ⟨halshs-01445907⟩

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