Structure and Dynamics of Micelle-bound Human α-Synuclein*
By T. Ulmer, A. Bax, N. Cole, R. Nussbaum. Journal of Biological Chemistry, 2005
682 citations recorded by the source corpus.
Misfolding of the protein α-synuclein (aS), which associates with presynaptic vesicles, has been implicated in the molecular chain of events leading to Parkinson's disease. Here, the structure and dynamics of micelle-bound aS are reported. Val3-Val37 and Lys45-Thr92 form curved α-helices, connected by a well ordered, extended linker in an unexpected anti-parallel arrangement, followed by another short extended region (Gly93-Lys97), overlapping the recently identified chaperone-mediated autophagy recognition motif and a highly mobile tail (Asp98-Ala140). Helix curvature is significantly less than predicted based on the native micelle shape, indicating a deformation of the micelle by aS. Structural and dynamic parameters show a reduced helical content for Ala30-Val37. A dynamic variation in interhelical distance on the microsecond timescale is complemented by enhanced sub-nanosecond timescale dynamics, particularly in the remarkably glycine-rich segments of the helices. These unusually rich dynamics may serve to mitigate the effect of aS binding on membrane fluidity. The well ordered conformation of the helix-helix connector indicates a defined interaction with lipidic surfaces, suggesting that, when bound to larger diameter synaptic vesicles, it can act as a switch between this structure and a previously proposed uninterrupted helix.
Subfields: Molecular Biology, Neurology, Physiology
View Paper: https://www.semanticscholar.org/paper/b69c59497500b5ca30d0c90fb0ddce7df10562c4
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Citations in the corpus
- Helix periodicity, topology, and dynamics of membrane‐associated α‐Synuclein (2005, methodology): “Ulmer et al. (2004) use a paramagnetic label at position 87 to detect a proximity between the two helical segments of aS, while our data, especially from samples spin-labeled at positions 72, 61, 20, and 9, do not show significant broadening at locations that would most closely approach them in the…”