1xq8: Difference between revisions
New page: left|200px<br /> <applet load="1xq8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xq8" /> '''Human micelle-bound alpha-synuclein'''<br /... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[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== | ||
| Line 11: | Line 10: | ||
==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== | ||
| Line 18: | Line 17: | ||
[[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
|
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.
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
