The Effects of Aggregation-Inducing Motifs on Amyloid Formation of Model Proteins Related to Neurodegenerative Diseases
详细信息 查看全文
- 作者：Motomasa Tanaka ; Yoko Machida ; Yukihiro Nishikawa ; Takumi Akagi ; Isao Morishima ; Tsutomu Hashikawa ; Tetsuro Fujisawa ; and Nobuyuki Nukina
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：August 13, 2002
- 年：2002
- 卷：41
- 期：32
- 页码：10277 - 10286
- 全文大小：235K
- 年卷期：v.41,no.32(August 13, 2002)
- ISSN：1520-4995
文摘
To examine the effects of aggregation-inducing motifs related to neurodegenerative diseaseson amyloid formation of host protein, we prepared several chimera myoglobins, in which variousaggregation-inducing motifs were inserted. The focused aggregation-inducing motifs included five (R5)or two (R2) oligopeptide repeats in yeast Sup35p, five octapeptide repeats (OPR) in the human prionprotein, a nonamyloid 
component (NAC) in 
-synuclein, and tandem repeats of 50 glutamines (Q50).Circular dichroism and infrared spectroscopies suggested that the OPR, R5, and Q50 motifs formed anantiparallel sheet as well as a random coil, whereas the R2 and NAC motifs mainly formed randomcoils. The OPR, R5, and Q50 mutants, but not the R2 and NAC mutants, readily formed the SDS-resistantaggregates under physiological condition, and electron microscopy revealed that the aggregates containedamyloid fibrils. The destabilization and increase in gyration radius of the OPR, R5, and Q50 mutantscorrelated with the tendency to form amyloid fibrils. A control mutant bearing a nonamyloidgenic sequencewas also moderately destabilized but did not form amyloid fibrils. Therefore, we concluded that the OPR,R5, and Q50 motifs, even in a quite stable protein such as myoglobin, led the host protein to formationof amyloid fibrils under physiological condition.
component (NAC) in -synuclein, and tandem repeats of 50 glutamines (Q50).Circular dichroism and infrared spectroscopies suggested that the OPR, R5, and Q50 motifs formed anantiparallel sheet as well as a random coil, whereas the R2 and NAC motifs mainly formed randomcoils. The OPR, R5, and Q50 mutants, but not the R2 and NAC mutants, readily formed the SDS-resistantaggregates under physiological condition, and electron microscopy revealed that the aggregates containedamyloid fibrils. The destabilization and increase in gyration radius of the OPR, R5, and Q50 mutantscorrelated with the tendency to form amyloid fibrils. A control mutant bearing a nonamyloidgenic sequencewas also moderately destabilized but did not form amyloid fibrils. Therefore, we concluded that the OPR,R5, and Q50 motifs, even in a quite stable protein such as myoglobin, led the host protein to formationof amyloid fibrils under physiological condition.