Terminal Alkynes as Raman Probes of α‐Synuclein in Solution and in Cells
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), mice...
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| Veröffentlicht in: | Chembiochem : a European journal of chemical biology 2020-06, Vol.21 (11), p.1582-1586 |
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| creator | Flynn, Jessica D. Gimmen, Megan Y. Dean, Dexter N. Lacy, Shannon M. Lee, Jennifer C. |
| description | 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.
Small but mighty: Small, terminal alkynes were biosynthetically incorporated into α‐synuclein as vibrational reporters. These bio‐orthogonal probes are very powerful in providing site‐specific information on protein conformational changes in cells, such as protein–lipid interactions. |
| doi_str_mv | 10.1002/cbic.202000026 |
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Small but mighty: Small, terminal alkynes were biosynthetically incorporated into α‐synuclein as vibrational reporters. These bio‐orthogonal probes are very powerful in providing site‐specific information on protein conformational changes in cells, such as protein–lipid interactions.</description><subject>Alkynes</subject><subject>Amino acids</subject><subject>amyloids</subject><subject>C-terminal truncations</subject><subject>Dopamine receptors</subject><subject>Fibrils</subject><subject>Heterogeneity</subject><subject>homopropargylglycine</subject><subject>Lipids</subject><subject>Micelles</subject><subject>Movement disorders</subject><subject>Neurodegenerative diseases</subject><subject>Parkinson's disease</subject><subject>Probes</subject><subject>Raman spectroscopy</subject><subject>Residues</subject><subject>Synuclein</subject><issn>1439-4227</issn><issn>1439-7633</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkc1OGzEUha0KRNKUbZfVSGy6SfBfPOMNEh3xpyJRNWFteTwecPDYwc6Asusj8Cp9kT4ET1JHCYF2g2XJvrqfj3zuAeAzgiMEIT5UlVEjDDFMC7MPoI8o4cOcEbKzuVOM8x74GOMsIZwRtAd6BHEGOSd98H2qQ2uctNmxvVs6HTMZs5-ylS77EXyVat9kf34__3qaLF2nrDYuS3vibbcw3mXS1au61NbGT2C3kTbq_c05ANenJ9PyfHh5dXZRHl8OFWUFG5KGSMk4lbqoixzCMVRjAsdUVhgjWOFVU9VIooowRVOPNEXdVE0yg5lCORmAo7XuvKtaXSvtFkFaMQ-mlWEpvDTi344zt-LGP4gcM14glgS-bgSCv-90XIjWRJUsSKd9FwUmlEBS8DShATj4D535LqR5JYrCguY8hzRRozWlgo8x6Gb7GQTFKiexyklsc0oPvry1sMVfgkkAXwOPxurlO3Ki_HZRvor_BRlbn9s</recordid><startdate>20200602</startdate><enddate>20200602</enddate><creator>Flynn, Jessica D.</creator><creator>Gimmen, Megan Y.</creator><creator>Dean, Dexter N.</creator><creator>Lacy, Shannon M.</creator><creator>Lee, Jennifer C.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2279-3393</orcidid><orcidid>https://orcid.org/0000-0003-0506-8349</orcidid><orcidid>https://orcid.org/0000-0002-9310-4882</orcidid></search><sort><creationdate>20200602</creationdate><title>Terminal Alkynes as Raman Probes of α‐Synuclein in Solution and in Cells</title><author>Flynn, Jessica D. ; 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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Alkynes Amino acids amyloids C-terminal truncations Dopamine receptors Fibrils Heterogeneity homopropargylglycine Lipids Micelles Movement disorders Neurodegenerative diseases Parkinson's disease Probes Raman spectroscopy Residues Synuclein |
| title | Terminal Alkynes as Raman Probes of α‐Synuclein in Solution and in Cells |
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