期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 42, 页码 17308-17313出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1106325108
关键词
prion disease; protein structure; protein dynamics; transmissible spongiform encephalopathy
资金
- Swiss National Science Foundation
- Eidgenossische Technische Hochschule Zurich through National Center of Competence in Research Structural Biology,
- European Union [512052]
In the otherwise highly conserved NMR structures of cellular prion proteins (PrPC) from different mammals, species variations in a surface epitope that includes a loop linking a beta-strand, beta 2, with a helix, alpha 2, are associated with NMR manifestations of a dynamic equilibrium between locally different conformations. Here, it is shown that this local dynamic conformational polymorphism in mouse PrPC is eliminated through exchange of Tyr169 by Ala or Gly, but is preserved after exchange of Tyr 169 with Phe. NMR structure determinations of designed variants of mouse PrP(121-231) at 20 degrees C and of wild-type mPrP(121-231) at 37 degrees C together with analysis of exchange effects on NMR signals then resulted in the identification of the two limiting structures involved in this local conformational exchange in wild-type mouse PrPC, and showed that the two exchanging structures present characteristically different solvent-exposed epitopes near the beta 2-alpha 2 loop. The structural data presented in this paper provided a platform for currently ongoing, rationally designed experiments with transgenic laboratory animals for renewed attempts to unravel the so far elusive physiological function of the cellular prion protein.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据