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1xq8
From Proteopedia
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[[Image:1xq8.gif|left|200px]] | [[Image:1xq8.gif|left|200px]] | ||
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'''Human micelle-bound alpha-synuclein''' | '''Human micelle-bound alpha-synuclein''' | ||
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[[Category: Nussbaum, R L.]] | [[Category: Nussbaum, R L.]] | ||
[[Category: Ulmer, T S.]] | [[Category: Ulmer, T S.]] | ||
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Revision as of 12:21, 3 May 2008
Human micelle-bound alpha-synuclein
Overview
Misfolding of the protein alpha-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 alpha-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.
About this Structure
1XQ8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and dynamics of micelle-bound human alpha-synuclein., Ulmer TS, Bax A, Cole NB, Nussbaum RL, J Biol Chem. 2005 Mar 11;280(10):9595-603. Epub 2004 Dec 22. PMID:15615727 Page seeded by OCA on Sat May 3 15:21:42 2008
