Pressure Reveals Unique Conformational Features in Prion Protein Fibril Diversity

被引:0
|
作者
Joan Torrent
Davy Martin
Sylvie Noinville
Yi Yin
Marie Doumic
Mohammed Moudjou
Vincent Béringue
Human Rezaei
机构
[1] Institut National de la Recherche Agronomique,
[2] UR892,undefined
[3] Virologie Immunologie Moléculaires,undefined
[4] Sorbonne Universités,undefined
[5] UPMC Univ Paris 06,undefined
[6] CNRS,undefined
[7] UMR8233,undefined
[8] MONARIS,undefined
[9] Université Pierre et Marie Curie,undefined
[10] Sorbonne Universités,undefined
[11] Inria,undefined
[12] UPMC Univ Paris 06,undefined
[13] CNRS,undefined
[14] UMR7598,undefined
[15] Lab. J.L. Lions,undefined
来源
Scientific Reports | / 9卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
The prion protein (PrP) misfolds and assembles into a wide spectrum of self-propagating quaternary structures, designated PrPSc. These various PrP superstructures can be functionally different, conferring clinically distinctive symptomatology, neuropathology and infectious character to the associated prion diseases. However, a satisfying molecular basis of PrP structural diversity is lacking in the literature. To provide mechanistic insights into the etiology of PrP polymorphism, we have engineered a set of 6 variants of the human protein and obtained PrP amyloid fibrils. We show that pressure induces dissociation of the fibrils, albeit with different kinetics. In addition, by focusing on the generic properties of amyloid fibrils, such as the thioflavin T binding capacities and the PK-resistance, we reveal an unprecedented structure-barostability phenomenological relationship. We propose that the structural diversity of PrP fibrils encompass a multiplicity of packing defects (water-excluded cavities) in their hydrophobic cores, and that the resultant sensitivity to pressure should be considered as a general molecular criterion to accurately define fibril morphotypes. We anticipate that our insights into sequence-dependent fibrillation and conformational stability will shed light on the highly-nuanced prion strain phenomenon and open the opportunity to explain different PrP conformations in terms of volumetric physics.
引用
收藏
相关论文
共 50 条
  • [21] Interplays Between Covalent Modifications in the Endoplasmic Reticulum Increase Conformational Diversity in Nascent Prion Protein
    Orsi, Andrea
    Sitia, Roberto
    PRION, 2007, 1 (04) : 236 - 242
  • [22] Compartment-Restricted Biotinylation Reveals Novel Features of Prion Protein Metabolism in Vivo
    Emerman, Amy B.
    Zhang, Zai-Rong
    Chakrabarti, Oishee
    Hegde, Ramanujan S.
    MOLECULAR BIOLOGY OF THE CELL, 2010, 21 (24) : 4325 - 4337
  • [23] A conformational switch controlling the toxicity of the prion protein
    Karl Frontzek
    Marco Bardelli
    Assunta Senatore
    Anna Henzi
    Regina R. Reimann
    Seden Bedir
    Marika Marino
    Rohanah Hussain
    Simon Jurt
    Georg Meisl
    Mattia Pedotti
    Federica Mazzola
    Giuliano Siligardi
    Oliver Zerbe
    Marco Losa
    Tuomas Knowles
    Asvin Lakkaraju
    Caihong Zhu
    Petra Schwarz
    Simone Hornemann
    Matthew G. Holt
    Luca Simonelli
    Luca Varani
    Adriano Aguzzi
    Nature Structural & Molecular Biology, 2022, 29 : 831 - 840
  • [24] Conformational plasticity of recombinant bovine prion protein
    V. B. Grigoriev
    S. L. Kalnov
    A. N. Pokidyshev
    S. M. Klimenko
    Doklady Biochemistry and Biophysics, 2010, 430 : 17 - 19
  • [25] Conformational transitions of the recombinant prion protein.
    Swietnicki, W
    Morillas, M
    Chen, SG
    Gambetii, P
    Surewicz, WK
    BIOPHYSICAL JOURNAL, 2000, 78 (01) : 13A - 13A
  • [26] Slow conformational dynamics in the hamster prion protein
    Kuwata, K
    Kamatari, YO
    Akasaka, K
    James, TL
    BIOCHEMISTRY, 2004, 43 (15) : 4439 - 4446
  • [27] A conformational switch controlling the toxicity of the prion protein
    Frontzek, Karl
    Bardelli, Marco
    Senatore, Assunta
    Henzi, Anna
    Reimann, Regina R.
    Bedir, Seden
    Marino, Marika
    Hussain, Rohanah
    Jurt, Simon
    Meisl, Georg
    Pedotti, Mattia
    Mazzola, Federica
    Siligardi, Giuliano
    Zerbe, Oliver
    Losa, Marco
    Knowles, Tuomas
    Lakkaraju, Asvin
    Zhu, Caihong
    Schwarz, Petra
    Hornemann, Simone
    Holt, Matthew G.
    Simonelli, Luca
    Varani, Luca
    Aguzzi, Adriano
    NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2022, 29 (08) : 831 - +
  • [28] Conformational plasticity of recombinant bovine prion protein
    Grigoriev, V. B.
    Kalnov, S. L.
    Pokidyshev, A. N.
    Klimenko, S. M.
    DOKLADY BIOCHEMISTRY AND BIOPHYSICS, 2010, 430 (01) : 17 - 19
  • [29] Conformational stability of human recombinant prion protein
    Swietnicki, W
    Morillas, M
    Surewicz, WK
    FASEB JOURNAL, 1999, 13 (07): : A1387 - A1387
  • [30] Unique Structural Features of Mule Deer Prion Protein Provide Insights into Chronic Wasting Disease
    Slapsak, Urska
    Salzano, Giulia
    Ilc, Gregor
    Giachin, Gabriele
    Bian, Jifeng
    Telling, Glenn
    Legname, Giuseppe
    Plavec, Janez
    ACS OMEGA, 2019, 4 (22): : 19913 - 19924