Syme, C.D. , Blanch, E.W., Holt, C., Jakes, R., Goedert, M., Hecht, L. and Barron, L.D. (2002) A Raman optical activity study of rheomorphism in caseins, synucleins and tau - New insight into the structure and behaviour of natively unfolded proteins. European Journal of Biochemistry, 269(1), pp. 148-156. (doi: 10.1046/j.0014-2956.2001.02633.x)
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Abstract
The casein milk proteins and the brain proteins α-synuclein and tau have been described as natively unfolded with random coil structures, which, in the case of α-synuclein and tau, have a propensity to form the fibrils found in a number of neurodegenerative diseases. New insight into the structures of these proteins has been provided by a Raman optical activity study, supplemented with differential scanning calorimetry, of bovine β- and κ-casein, recombinant human α-, β- and γ-synuclein, together with the A30P and A53T mutants of α -synuclein associated with familial cases of Parkinson's disease, and recombinant human tau46 together with the tau46 P301L mutant associated with inherited frontotemporal dementia. The Raman optical activity spectra of all these proteins are very similar, being dominated by a strong positive band centred at ≈ 1318 cm<sup>−1</sup> that may be due to the poly(l-proline) II (PPII) helical conformation. There are no Raman optical activity bands characteristic of extended secondary structure, although some unassociated β strand may be present. Differential scanning calorimetry revealed no thermal transitions for these proteins in the range 15–110 °C, suggesting that the structures are loose and noncooperative. As it is extended, flexible, lacks intrachain hydrogen bonds and is hydrated in aqueous solution, PPII helix may impart a rheomorphic (flowing shape) character to the structure of these proteins that could be essential for their native function but which may, in the case of α-synuclein and tau, result in a propensity for pathological fibril formation due to particular residue properties.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Syme, Dr Christopher and Hecht, Dr Lutz and Barron, Professor Laurence |
| Authors: | Syme, C.D., Blanch, E.W., Holt, C., Jakes, R., Goedert, M., Hecht, L., and Barron, L.D. |
| College/School: | College of Science and Engineering > School of Chemistry |
| Journal Name: | European Journal of Biochemistry |
| Publisher: | Wiley-Blackwell Publishing Ltd. |
| ISSN: | 1742-464X |
| ISSN (Online): | 1742-4658 |
| Published Online: | 30 October 2003 |
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