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PDBsum entry 1xq8

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Lipid binding protein PDB id
1xq8
Jmol
Contents
Protein chain
140 a.a.

References listed in PDB file
Key reference
Title Structure and dynamics of micelle-Bound human alpha-Synuclein.
Authors T.S.Ulmer, A.Bax, N.B.Cole, R.L.Nussbaum.
Ref. J Biol Chem, 2005, 280, 9595-9603. [DOI no: 10.1074/jbc.M411805200]
PubMed id 15615727
Abstract
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.
Figure 1.
FIG. 1. Amino acid sequence of human -synuclein (aS). The seven imperfect 11-residue repeats are labeled in Roman numerals with their second to sixth residues (predominantly KTKEGV) highlighted in red. Ser9-Ala^89 are referred to as the "repeat region" and Asp98-Ala^140 as the "tail region" of aS. Residues found to be in helical conformation in micelle-bound aS are underlined.
Figure 7.
FIG. 7. Charge distribution of micelle-bound aS. A and B, top and bottom view of the molecular surface of micelle-bound aS (average structure; Fig. 4, C-E) color-coded by electrostatic potential as depicted. The predominantly unstructured tail of aS is shown to contrast its highly acidic nature with the repeat region of aS. Electrostatic potential was calculated with APBS (70).
The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 9595-9603) copyright 2005.
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