Interrogating the Dimerization Interface of the Prion Protein Via Site-Specific Mutations to p-Benzoyl-L-Phenylalanine

Sangeetham, Sudheer Babu and Huszár, Krisztina and Bencsura, Petra and Nyeste, Antal and Hunyadi-Gulyás Éva, Csilla and Ayaydin-Fodor, Elfrieda and Welker, Ervin (2018) Interrogating the Dimerization Interface of the Prion Protein Via Site-Specific Mutations to p-Benzoyl-L-Phenylalanine. JOURNAL OF MOLECULAR BIOLOGY, 430 (17). pp. 2784-2801. ISSN 0022-2836


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Transmissible spongiform encephalopathies are centered on the conformational transition of the prion protein from a mainly helical, monomeric structure to a beta-sheet rich ordered aggregate. Experiments indicate that the main infectious and toxic species in this process are however shorter oligomers, formation of which from the monomers is yet enigmatic. Here, we created 25 variants of the mouse prion protein site-specifically containing one genetically-incorporated para-benzoyl-phenylalanine (pBpa), a cross-linkable non-natural amino acid, in order to interrogate the interface of a prion protein-dimer, which might lie on the pathway of oligomerization. Our results reveal that the N-terminal part of the prion protein, especially regions around position 127 and 107, is integral part of the dimer interface. These together with additional pBpa-containing variants of mPrP might also facilitate to gain more structural insights into oligomeric and fibrillar prion protein species including the pathological variants. (C) 2018 Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: MASS-SPECTROMETRY; CROSS-LINKING; Dimerization; Thermodynamic stability; conformational transition; red fluorescent protein; prion; NMR CHARACTERIZATION; TERMINAL FRAGMENT; CYCLIC AMPLIFICATION; CELL-FREE FORMATION; AMYLOID FIBRIL FORMATION; Protein conformational stability; pBpa; Photo-crosslinking;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
Depositing User: MTMT SWORD
Date Deposited: 31 Jan 2019 16:59
Last Modified: 31 Jan 2019 16:59

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