Many amyloid fibrils associated with neurodegenerative
diseases
consist of an ordered fibril core (FC) and disordered terminal regions
(TRs). The former represents a stable scaffold, while the latter is
rather active in binding with various partners. Current structural
studies mainly focus on the ordered FC since the high flexibility
of TRs hinders structural characterization. Here, by combining insensitive
nuclei enhanced by polarization transfer-based 1H-detected
solid-state NMR and cryo-EM, we explored the intact structure of an
α-syn fibril including both FC and TRs and further studied the
conformational dynamics of the fibril upon binding to lymphocyte activation
gene 3 (LAG3)a cell surface receptor that is involved in α-syn
fibril transmission in brains. We found that both the N- and C-TRs
of α-syn are disordered in free fibrils featuring similar conformation
ensembles as those in soluble monomers. While in the presence of the
D1 domain of LAG3 (L3D1), the C-TR directly binds to L3D1, meanwhile
the N-TR folds into a β-strand and further integrates with the
FC, which leads to alteration of the overall fibril structure and
surface property. Our work reveals synergistic conformational transition
of the intrinsically disordered TRs of α-syn, which sheds light
on mechanistic understanding of the essential role of TRs in regulating
the structure and pathology of amyloid fibrils.
The electrochemical behavior of UO 2 F 2 in LiF-NaF-KF (46.5-11.5-42 mol%, FLiNaK) melt on Pt electrode was investigated at 550 • C by cyclic voltammetry (CV) and square wave voltammetry (SWV). UO 2 F 2 was prepared by the reaction of UF 4 powder and oxygen at 650 • C, and ascertained by X-ray diffraction (XRD) and Raman spectroscopy. It was found that the reduction of UO 2 2+ in FLiNaK exhibited two steps both with one exchanged electron: UO 2 2+ + e − → UO 2 + and UO 2 + + e − → UO 2 , with the CV reduction peak at about 2.02 V and 1.49 V (vs. K + /K), respectively. Both of them were reversible and diffusion-controlled. By means of potentiostatic electrolysis, the product of UO 2 was obtained and the separation ratio of uranium from UO 2 F 2 -FLiNaK melt was approximately 54.5% at 550 • C, which were characterized by XRD and the inductively coupled plasma atomic emission spectrometer (ICP-AES).
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