The N-Terminal Repeat Domain of -Synuclein Inhibits 
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- 作者：Jeffrey C. Kessler ; Jean-Christophe Rochet ; and Peter T. Lansbury ; Jr.
- 刊名：Biochemistry
- 出版年：2003
- 出版时间：January 28, 2003
- 年：2003
- 卷：42
- 期：3
- 页码：672 - 678
- 全文大小：238K
- 年卷期：v.42,no.3(January 28, 2003)
- ISSN：1520-4995
文摘
The conversion of 
-synuclein into amyloid fibrils in the substantia nigra is linked toParkinson's disease. -Synuclein is natively unfolded in solution, but can be induced to form either -helicalor 
-sheet structure depending on its concentration and the solution conditions. The N-terminus of-synuclein comprises seven 11-amino acid repeats (XKTKEGVXXXX) which can form an amphipathic-helix. Why seven repeats, rather than six or eight, survived the evolutionary process is not clear. Toprobe this question, two sequence variants of -synuclein, one with two fewer (del2) and one with twoadditional (plus2) repeats, were studied. As compared to wild-type -synuclein, the plus2 variant disfavorsthe formation of -sheet-rich oligomers, including amyloid fibrils. In contrast, the truncated variant, del2,favors -sheet and fibril formation. We propose that the repeat number in WT -synuclein represents anevolutionary balance between the functional conformer of -synuclein (-helix and/or random coil) andits pathogenic -sheet conformation. N-Terminal truncation of -synuclein may promote pathogenesis.
-synuclein into amyloid fibrils in the substantia nigra is linked toParkinson's disease. -Synuclein is natively unfolded in solution, but can be induced to form either -helicalor -sheet structure depending on its concentration and the solution conditions. The N-terminus of-synuclein comprises seven 11-amino acid repeats (XKTKEGVXXXX) which can form an amphipathic-helix. Why seven repeats, rather than six or eight, survived the evolutionary process is not clear. Toprobe this question, two sequence variants of -synuclein, one with two fewer (del2) and one with twoadditional (plus2) repeats, were studied. As compared to wild-type -synuclein, the plus2 variant disfavorsthe formation of -sheet-rich oligomers, including amyloid fibrils. In contrast, the truncated variant, del2,favors -sheet and fibril formation. We propose that the repeat number in WT -synuclein represents anevolutionary balance between the functional conformer of -synuclein (-helix and/or random coil) andits pathogenic -sheet conformation. N-Terminal truncation of -synuclein may promote pathogenesis.