1xq8

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Revision as of 18:03, 12 November 2007

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Human micelle-bound alpha-synuclein

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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.

Disease

Known diseases associated with this structure: Dementia, Lewy body OMIM:[163890], Parkinson disease 4, autosomal dominant Lewy body OMIM:[163890], Parkinson disease, familial OMIM:[163890]

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

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