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Unique Structural Characteristics of the Rabbit Prion Protein
Wen, Yi( Chinese Acad Sci, Shanghai Inst Mat Med) ; Li, Jun( Chinese Acad Sci, Shanghai Inst Mat Med) ; Yao, Wenming( Chinese Acad Sci, Shanghai Inst Mat Med) ; Xiong, Minqian( Chinese Acad Sci, Shanghai Inst Mat Med) ; Hong, Jing( Chinese Acad Sci, Shanghai Inst Mat Med) ; Peng, Yu( Chinese Acad Sci, Shanghai Inst Mat Med) ; Xiao, Gengfu(Wuhan Univ, Coll Life Sci) ; Lin, Donghai ; Lin DH(林东海)
2010-07-16
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.; National Natural Science Foundation of China [30730026, 30570352]; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China [2009ZX09301-001]
语种英语
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
内容类型期刊论文
源URL[http://dx.doi.org/doi:10.1074/jbc.M110.118844]  
专题化学化工-已发表论文
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GB/T 7714
Wen, Yi,Li, Jun,Yao, Wenming,et al. Unique Structural Characteristics of the Rabbit Prion Protein[J],2010.
APA Wen, Yi.,Li, Jun.,Yao, Wenming.,Xiong, Minqian.,Hong, Jing.,...&林东海.(2010).Unique Structural Characteristics of the Rabbit Prion Protein..
MLA Wen, Yi,et al."Unique Structural Characteristics of the Rabbit Prion Protein".(2010).
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