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	Nanoscale observation of heparin-mediated self-assembly of chiral tau enantiomers
	Chen, Wei1,2,3; Chen, Yunhao1,2; Chen, Ligang1,2,3; Zhou, Shuo1,2; Li, Dandan1,3; Yin, Bohua1,2; Yang, Zhongbo1,2,3; Wang, Liang1,2; Wang, Huabin1,2,3
	2024-03-01
摘要	Understanding the effects of chirality and cofactors on neuropathogenic protein self-assembly has garnered much attention due to its close relevance with neuro-degenerative diseases. However, hitherto chiral Tau self-assembly and cofactors-mediated chiral Tau self-assembly are unexplored terrains. In this communication, we report the observation of self-assembly of synthesized natural levorotary (L-) enantiomer and its mirror image-dextrorotary (D-) enantiomer of a crucial Tau fragment (residues 391-426), as well as heparin-mediated selfassembly of these Tau enantiomers, with atomic force microscopy (AFM) and a biological nanopore sensor. The combination of the two techniques allows us to visually and electrochemically monitor the self-assembly behaviors. We observe that L-Tau enantiomers have a slight tendency to form small fibril aggregates while D-Tau enantiomers tend to form densely packed fibril aggregates. Interestingly, heparin mediates L-Tau enantiomers to form right-handed twisted polymorphic fibrils with pronounced fibril aggregates coexisting, but mediates D-Tau enantiomers to form abundant left-handed twisted polymorphic fibrils with sparse aggregates coexisting. Circular dichroism spectra indicate rich /3-sheets formed in either assembly of heparin-mediated Tau enantiomers. The above observations manifest the significant effects of chirality and cofactor (i.e., heparin) on the selfassembly of Tau enantiomers. Collectively, this work sheds new insights into the regulation of Tau selfassembly by chirality and cofactors, and proves the combination of AFM with a biological nanopore sensor an effective biophysical platform for label-free and high-definition study of protein self-assembly.
关键词	Chirality Heparin Tau Self-assembly Atomic force microscopy Nanopore
DOI	10.1016/j.mtphys.2024.101370
发表期刊	MATERIALS TODAY PHYSICS
ISSN	2542-5293
卷号	42页码:7
通讯作者	Wang, Liang(wangliang83@cigit.ac.cn) ; Wang, Huabin(wanghuabin@cigit.ac.cn)
收录类别	SCI
WOS记录号	WOS:001186732800001
语种	en