Unique Structural Characteristics of the Rabbit Prion Protein

doi:10.1074/jbc.M110.118844

	Unique Structural Characteristics of the Rabbit Prion Protein
	Wen, Yi 1; Li, Jun1 ; Yao, Wenming 1; Xiong, Minqian 1; Hong, Jing 1; Peng, Yu 1; Xiao, Gengfu 2; Lin, Donghai 1,3
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	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.
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
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000282764600060
内容类型	期刊论文
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.