WT and A53T α-Synuclein Systems: Melting Diagram and Its New Interpretation

International Journal of Molecular Sciences

Kyou-Hoon Han¹  Kálmán Tompa²  Mónika Bokor²  Ágnes Tantos³  Péter Tompa³ 

[1] BioMedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Rucheng District, Dade District 305 333, Korea;Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, 1121 Budapest, Hungary;Institute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, Hungary;

关键词: NMR spectroscopy;    bond energy;    hydration;    proteins;    aggregation;   

DOI  :  10.3390/ijms21113997

来源: DOAJ

【 摘 要 】

The potential barriers governing the motions of α-synuclein (αS) variants’ hydration water, especially energetics of them, is in the focus of the work. The thermodynamical approach yielded essential information about distributions and heights of the potential barriers. The proteins’ structural disorder was measured by ratios of heterogeneous water-binding interfaces. They showed the αS monomers, oligomers and amyloids to possess secondary structural elements, although monomers are intrinsically disordered. Despite their disordered nature, monomers have 33% secondary structure, and therefore they are more compact than a random coil. At the lowest potential barriers with mobile hydration water, monomers are already functional, a monolayer of mobile hydration water is surrounding them. Monomers realize all possible hydrogen bonds with the solvent water. αS oligomers and amyloids have half of the mobile hydration water amount than monomers because aggregation involves less mobile hydration. The solvent-accessible surface of the oligomers is ordered or homogenous in its interactions with water to 66%. As a contrast, αS amyloids are disordered or heterogeneous to 75% of their solvent accessible surface and both wild type and A53T amyloids show identical, low-level hydration. Mobile water molecules in the first hydration shell of amyloids are the weakest bound compared to other forms.

【 授权许可】

Unknown