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Terminal Alkynes as Raman Probes of α‐Synuclein in Solution and in Cells
Author(s) -
Flynn Jessica D.,
Gimmen Megan Y.,
Dean Dexter N.,
Lacy Shan M.,
Lee Jennifer C.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000026
Subject(s) - raman spectroscopy , chemistry , biophysics , terminal (telecommunication) , amide , fibril , stereochemistry , biochemistry , biology , physics , optics , telecommunications , computer science
Conformational changes in α‐synuclein (α‐syn) are central to its biological function and Parkinson's disease pathology. Here, terminal alkynes (homopropargylglycine) were employed as environmentally sensitive Raman probes at residues 1, 5, 116, and 127 to characterize soluble (disordered), micelle‐bound (α‐helical), and fibrillar (β‐sheet) α‐syn. Along with the full‐length protein, a disease‐related C‐terminal truncation (1–115) was also studied. For the first time, β‐sheet α‐syn amyloid structure was detected by the amide‐I band in N27 dopaminergic rat cells, where a reciprocal relationship between levels of fibrils and lipids was seen. Site‐specific spectral features of the terminal alkynes also revealed the heterogeneity of the cellular environment. This work shows the versatility of Raman microspectroscopy and the power of unnatural amino acids in providing structural and residue‐level insights in solution and in cells.