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1xq8
From Proteopedia
(New page: 200px<br /> <applet load="1xq8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xq8" /> '''Human micelle-bound alpha-synuclein'''<br /...) |
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| - | [[Image:1xq8.gif|left|200px]]<br /> | + | [[Image:1xq8.gif|left|200px]]<br /><applet load="1xq8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xq8" size=" | + | |
caption="1xq8" /> | caption="1xq8" /> | ||
'''Human micelle-bound alpha-synuclein'''<br /> | '''Human micelle-bound alpha-synuclein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Misfolding of the protein alpha-synuclein (aS), which associates with | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1XQ8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1XQ8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XQ8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bax, A.]] | [[Category: Bax, A.]] | ||
| - | [[Category: Cole, N | + | [[Category: Cole, N B.]] |
| - | [[Category: Nussbaum, R | + | [[Category: Nussbaum, R L.]] |
| - | [[Category: Ulmer, T | + | [[Category: Ulmer, T S.]] |
[[Category: micelle-bound helix]] | [[Category: micelle-bound helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:57:29 2008'' |
Revision as of 13:57, 21 February 2008
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Human micelle-bound alpha-synuclein
Contents |
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
Page seeded by OCA on Thu Feb 21 15:57:29 2008
