scholarly journals Nonpolar Substitution at the C-Terminus of the Prion Protein, a Mimic of the Glycosylphosphatidylinositol Anchor, Partially Impairs Amyloid Fibril Formation†

Biochemistry ◽  
2007 ◽  
Vol 46 (3) ◽  
pp. 852-861 ◽  
Author(s):  
Leonid Breydo ◽  
Ying Sun ◽  
Natallia Makarava ◽  
Cheng-I Lee ◽  
Vera Novitskaia ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Protein A ◽  
Fibril Formation ◽  
Glycosylphosphatidylinositol Anchor ◽  
C Terminus ◽  
Amyloid Fibril Formation

Structural mechanisms of oligomer and amyloid fibril formation by the prion protein

2018 ◽  
Vol 54 (49) ◽  
pp. 6230-6242 ◽  
Author(s):  
Ishita Sengupta ◽  
Jayant B. Udgaonkar
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Aggregation Mechanism ◽  
Amyloid Fibril Formation ◽  
Structural Mechanisms

The aggregation mechanism of the prion protein is highly heterogeneous.

Aggregation and Amyloid Fibril Formation of the Prion Protein Is Accelerated in the Presence of Glycogen

2008 ◽  
Vol 11 (2) ◽  
pp. 365-369 ◽  
Author(s):  
Giannantonio Panza ◽  
Jan Stöhr ◽  
Eva Birkmann ◽  
Detlev Riesner ◽  
Dieter Willbold ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation

scholarly journals Higher susceptibility to amyloid fibril formation of the recombinant ovine prion protein modified by transglutaminase

2012 ◽  
Vol 1822 (10) ◽  
pp. 1509-1515 ◽  
Author(s):  
Angela Sorrentino ◽  
Concetta Valeria L. Giosafatto ◽  
Ivana Sirangelo ◽  
Carmela De Simone ◽  
Prospero Di Pierro ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation

scholarly journals Conformational distortion in a fibril-forming oligomer arrests alpha-Synuclein fibrillation and minimizes its toxic effects

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ritobrita Chakraborty ◽  
Sandip Dey ◽  
Pallabi Sil ◽  
Simanta Sarani Paul ◽  
Dipita Bhattacharyya ◽  
...  
Keyword(s):  
Small Molecule ◽  
Solid State Nmr ◽  
Amyloid Fibril ◽  
Alpha Synuclein ◽  
Fibril Formation ◽  
Stoichiometric Ratio ◽  
Oligomeric State ◽  
C Terminus ◽  
Amyloid Fibril Formation ◽  
Oligomeric Forms

AbstractThe fibrillation pathway of alpha-Synuclein, the causative protein of Parkinson’s disease, encompasses transient, heterogeneous oligomeric forms whose structural understanding and link to toxicity are not yet understood. We report that the addition of the physiologically-available small molecule heme at a sub-stoichiometric ratio to either monomeric or aggregated α-Syn, targets a His50 residue critical for fibril-formation and stabilizes the structurally-heterogeneous populations of aggregates into a minimally-toxic oligomeric state. Cryo-EM 3D reconstruction revealed a ‘mace’-shaped structure of this monodisperse population of oligomers, which is comparable to a solid-state NMR Greek key-like motif (where the core residues are arranged in parallel in-register sheets with a Greek key topology at the C terminus) that forms the fundamental unit/kernel of protofilaments. Further structural analyses suggest that heme binding induces a distortion in the Greek key-like architecture of the mace oligomers, which impairs their further appending into protofilaments and fibrils. Additionally, our study reports a novel mechanism of prevention as well as reclamation of amyloid fibril formation by blocking an inter-protofilament His50 residue using a small molecule.

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