Unique Structural Characteristics of the Rabbit Prion Protein
文献类型：期刊论文
| 作者 | Wen, Yi1; Li, Jun1 ; Yao, Wenming1; Xiong, Minqian1; Hong, Jing1; Peng, Yu1; Xiao, Gengfu2; Lin, Donghai1,3
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2010-10-08 |
| 卷号 | 285期号:41页码:31682-31693 |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M110.118844 |
| 文献子类 | Article |
| 英文摘要 | Rabbits are one of the few mammalian species that appear to be resistant to transmissible spongiform encephalopathies due to the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here, we determined the solution structures of the recombinant protein RaPrPC-(91-228) and its S173N variant and detected the backbone dynamics of their structured C-terminal domains-(121-228). In contrast to many other mammalian PrP(C)s, loop 165-172, which connects beta-sheet-2 and alpha-helix-2, is well-defined in RaPrPC. For the first time, order parameters S-2 are obtained for residues in this loop region, indicating that loop 165-172 of RaPrPC is highly ordered. Compared with the wild-type RaPrPC, less hydrogen bonds form in the S173N variant. The NMR dynamics analysis reveals a distinct increase in the structural flexibility of loop 165-172 and helix-3 after the S173N substitution, implying that the S173N substitution disturbs the long range interaction of loop 165-172 with helix-3, which further leads to a marked decrease in the global conformational stability. Significantly, RaPrPC possesses a unique charge distribution, carrying a continuous area of positive charges on the surface, which is distinguished from other PrP(C)s. The S173N substitution causes visible changes of the charge distribution around the recognition sites for the hypothetical protein X. Our results suggest that the ordered loop 165-172 and its interaction with helix-3, together with the unique distribution of surface electrostatic potential, significantly contribute to the unique structural characteristics of RaPrPC. |
| WOS关键词 | NUCLEAR-MAGNETIC-RESONANCE ; N-15 NMR RELAXATION ; MODEL-FREE APPROACH ; LINEAR EXTRAPOLATION METHOD ; SPECTRAL DENSITY-FUNCTIONS ; MOLECULAR-DYNAMICS ; SYNTHETIC PEPTIDES ; BACKBONE DYNAMICS ; SCRAPIE ISOFORM ; SPIN-RELAXATION |
| 资助项目 | National Natural Science Foundation of China[30730026] ; National Natural Science Foundation of China[30570352] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2009ZX09301-001] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000282764600060 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278748]  |
| 专题 | 分析化学研究室 |
| 通讯作者 | Lin, Donghai |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, NMR Lab, Shanghai 201203, Peoples R China; 2.Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China; 3.Xiamen Univ, Coll Chem & Chem Engn, Key Lab Chem Biol Fujian Prov, Xiamen 361005, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wen, Yi,Li, Jun,Yao, Wenming,et al. Unique Structural Characteristics of the Rabbit Prion Protein[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2010,285(41):31682-31693. |
| APA | Wen, Yi.,Li, Jun.,Yao, Wenming.,Xiong, Minqian.,Hong, Jing.,...&Lin, Donghai.(2010).Unique Structural Characteristics of the Rabbit Prion Protein.JOURNAL OF BIOLOGICAL CHEMISTRY,285(41),31682-31693. |
| MLA | Wen, Yi,et al."Unique Structural Characteristics of the Rabbit Prion Protein".JOURNAL OF BIOLOGICAL CHEMISTRY 285.41(2010):31682-31693. |
入库方式： OAI收割
来源：上海药物研究所
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