5YJ5

structure for wildtype Human prion protein (M129)

5YJ5 の概要

• エントリーDOI: 10.2210/pdb5yj5/pdb
• NMR情報: BMRB: 36123
• 分子名称: Major prion protein (1 entity in total)
• 機能のキーワード: prion disease, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16243.14

構造登録者

Zheng, Z.,Lin, D. (登録日: 2017-10-08, 公開日: 2018-04-11, 最終更新日: 2024-11-13)

主引用文献

Zheng, Z.,Zhang, M.,Wang, Y.,Ma, R.,Guo, C.,Feng, L.,Wu, J.,Yao, H.,Lin, D.
Structural basis for the complete resistance of the human prion protein mutant G127V to prion disease.
Sci Rep, 8:13211-13211, 2018

PubMed Abstract: Prion diseases are caused by the propagation of misfolded cellular prion proteins (PrPs). A completely prion disease-resistant genotype, V127M129, has been identified in Papua New Guinea and verified in transgenic mice. To disclose the structural basis of the disease-resistant effect of the G127V mutant, we determined and compared the structural and dynamic features of the G127V-mutated human PrP (residues 91-231) and the wild-type PrP in solution. HuPrP(G127V) contains α1, α2 and α3 helices and a stretch-strand (SS) pattern comprising residues Tyr128-Gly131 (SS1) and Val161-Arg164 (SS2), with extending atomic distances between the SS1 and SS2 strands, and a structural rearrangement of the Tyr128 side chain due to steric hindrance of the larger hydrophobic side chain of Val127. The extended α1 helix gets closer to the α2 and α3 helices. NMR dynamics analysis revealed that Tyr128, Gly131 and Tyr163 underwent significant conformational exchanges. Molecular dynamics simulations suggest that HuPrP(G127V) prevents the formation of stable β-sheets and dimers. Unique structural and dynamic features potentially inhibit the conformational conversion of the G127V mutant. This work is beneficial for understanding the molecular mechanisms underlying the complete resistance of the G127V mutant to prion disease and for developing new therapeutics for prion disease.

PubMed: 30181558
DOI: 10.1038/s41598-018-31394-6

実験手法

SOLUTION NMR