New Concept on the Phase Space of the Protein : Experiments and Theory

蛋白质相空间的新概念:实验与理论

基本信息

批准号：
14380314
负责人：
KUWATA Kazuo
金额：
$ 9.41万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

We found and structurally characterized the folding intermediate of hamster prion protein using high-pressure NMR method (K.Kuwata, Biochemistry, 2002) and designated it as PrP^*. We found that in PrP^*, B-and C-helices are preferentially disordered, while A-helix remains intact. Especially residues locate at the interface with the beta sheet (S2) are extremely unstable. It is highly possible that partially unfolded PrP^* is involved in the structural conversion reaction from PrP^C to PrP^<Sc>.We also clarified the three dimensional structure of oligomeric duster of PrP106-126, a peptide corresponding to the hydrophobic cluster of prion protein, using electron microscopy, circular dichroism, NMR and molecular dynamics simulation (K Kuwata Proc.Natl.Acad.Sci, 2003). The oligomeric conformation of PrP106-126 dusterwas stabilized by the hydrophobic interaction between methyl moieties.In hamster prion, residues exchanging on a time scale of micro-to milliseconds using CPMG relaxation dispersion method some what correspond to those exhibit low stability in high-pressure NMR method (Kuwata et al., Biochemistry, 2004). Moreover the distribution of those unstable residues is correlated with those involved in the causative mutation. Thus these residues may be responsible for the conformational conversion from PrPC to PrP^<Sc>.Furthermore we formulated a novel mathematical representation of the protein dynamics using the number theoretical description.

我们使用高压NMR方法（K.Kuwata，Biiochemistry，2002）发现并在结构上表征了仓鼠prion蛋白的折叠中间体，并将其指定为PRP^*。我们发现，在Prp^*中，B-and C螺旋优先是无序的，而A-螺旋仍然完好无损。特别是残留物位于与Beta表（S2）界面处的残留物非常不稳定。很有可能部分展开的PRP^*参与了从PRP^C到PRP^<sc>的结构转化反应。我们还阐明了PRP106-126的寡聚duster的三维结构，一种对应于Prion Protein的Prion Protein的液生物群的肽，使用电子显微镜，NMREC，NMR和MORREC，NMRRISC，NMRRISC，NMRRISC，NMR和MOREC，摩尔氏蛋白proc.natl.acad.sci，2003年）。 The oligomeric conformation of PrP106-126 dusterwas stabilized by the hydrophobic interaction between methyl moieties.In hamster prion, residues exchanging on a time scale of micro-to milliseconds using CPMG relaxation dispersion method some what correspond to those exhibit low stability in high-pressure NMR method (Kuwata et al., Biochemistry, 2004).此外，这些不稳定残基的分布与参与因果突变的那些分布相关。因此，这些残基可能负责从PRPC到PRP^<sc>的构象转化。Furthermore我们使用数字理论描述对蛋白质动力学进行了新的数学表示。