铜抑制传染性朊病毒转化的机制。
A mechanism for copper inhibition of infectious prion conversion.
作者信息
Cox Daniel L, Pan Jianping, Singh Rajiv R P
出版信息
Biophys J. 2006 Jul 15;91(2):L11-3. doi: 10.1529/biophysj.106.083642. Epub 2006 May 12.
Abstract
We employ ab initio electronic structure calculations to obtain two structural models for copper bound in the strongest binding site of the noninfectious form of the prion protein. The models are compatible with available experimental constraints from electron spin resonance data. The bending of the peptide backbone attendant with the copper binding is not compatible with the requisite straight beta-strand backbone structure for the same sequence contained in two recently proposed models of the prion protein structure in its infectious form. We hypothesize that copper binding at this site is protective against conversion to the infectious form, discuss experimental data that appear to support and conflict with our hypothesis, and propose tests using recombinant prion protein, genetically modified cultured neurons, and transgenic mice.
摘要
我们采用从头算电子结构计算方法，来获取朊病毒蛋白非感染性形式最强结合位点处铜的两种结构模型。这些模型与电子自旋共振数据的现有实验约束条件相符。铜结合时伴随的肽主链弯曲，与朊病毒蛋白感染性形式的两种最近提出的结构模型中相同序列所需的直β-链主链结构不兼容。我们推测该位点的铜结合可防止转化为感染性形式，讨论了似乎支持和与我们的假设相矛盾的实验数据，并提出了使用重组朊病毒蛋白、基因改造的培养神经元和转基因小鼠进行测试的方案。
相似文献
1
A mechanism for copper inhibition of infectious prion conversion.
Biophys J. 2006 Jul 15;91(2):L11-3. doi: 10.1529/biophysj.106.083642. Epub 2006 May 12.
2
The cellular prion protein: biochemistry, topology, and physiologic functions.
Cell Biochem Biophys. 2003;38(3):287-304. doi: 10.1385/cbb:38:3:287.
3
Copper and Zinc Interactions with Cellular Prion Proteins Change Solubility of Full-Length Glycosylated Isoforms and Induce the Occurrence of Heterogeneous Phenotypes.
PLoS One. 2016 Apr 19;11(4):e0153931. doi: 10.1371/journal.pone.0153931. eCollection 2016.
4
Strain-specific prion-protein conformation determined by metal ions.
Nat Cell Biol. 1999 May;1(1):55-9. doi: 10.1038/9030.
5
Copper binding to the PrP isoforms: a putative marker of their conformation and function.
J Virol. 2001 Sep;75(17):7872-4. doi: 10.1128/jvi.75.17.7872-7874.2001.
6
Revisit the effect of fibrillization on functions of prion protein from the perspective of Cu(II) binding.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):32-37. doi: 10.1016/j.bbrc.2018.05.118. Epub 2018 Jun 11.
7
Plasminogen activation is stimulated by prion protein and regulated in a copper-dependent manner.
Biochemistry. 2002 Jun 4;41(22):6891-6. doi: 10.1021/bi025676g.
8
A receptor for infectious and cellular prion protein.
Braz J Med Biol Res. 1999 Jul;32(7):853-9. doi: 10.1590/s0100-879x1999000700009.
9
Cholesterol transporter ATP-binding cassette A1 (ABCA1) is elevated in prion disease and affects PrPC and PrPSc concentrations in cultured cells.
J Gen Virol. 2008 Jun;89(Pt 6):1525-1532. doi: 10.1099/vir.0.83358-0.
10
Folding and misfolding of the prion protein in the secretory pathway.
Amyloid. 2004 Sep;11(3):162-72. doi: 10.1080/1350-6120400000723.
引用本文的文献
1
Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.
Molecules. 2022 Jan 21;27(3):705. doi: 10.3390/molecules27030705.
2
Using NMR spectroscopy to investigate the role played by copper in prion diseases.
Neurol Sci. 2020 Sep;41(9):2389-2406. doi: 10.1007/s10072-020-04321-9. Epub 2020 Apr 24.
3
Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.
PLoS One. 2017 Dec 8;12(12):e0188989. doi: 10.1371/journal.pone.0188989. eCollection 2017.
4
The non-octarepeat copper binding site of the prion protein is a key regulator of prion conversion.
Sci Rep. 2015 Oct 20;5:15253. doi: 10.1038/srep15253.
5
Mechanism of copper(II)-induced misfolding of Parkinson's disease protein.
Sci Rep. 2011;1:11. doi: 10.1038/srep00011. Epub 2011 Jun 14.
6
Insights into prion protein function from atomistic simulations.
Prion. 2010 Jan-Mar;4(1):13-9. doi: 10.4161/pri.4.1.10969. Epub 2010 Jan 16.
7
Copper binding extrinsic to the octarepeat region in the prion protein.
Curr Protein Pept Sci. 2009 Oct;10(5):529-35. doi: 10.2174/138920309789352056.
8
Prion stability and infectivity in the environment.
Neurochem Res. 2009 Jan;34(1):158-68. doi: 10.1007/s11064-008-9741-6. Epub 2008 May 16.
9
Studying the Cu binding sites in the PrP N-terminal region: a test case for ab initio simulations.
Eur Biophys J. 2007 Sep;36(7):841-5. doi: 10.1007/s00249-007-0162-2. Epub 2007 May 10.
10
Probing structural differences in prion protein isoforms by tyrosine nitration.
Biochemistry. 2007 Apr 24;46(16):4850-60. doi: 10.1021/bi0617254. Epub 2007 Mar 31.
本文引用的文献
1
The SIESTA method; developments and applicability.
J Phys Condens Matter. 2008 Feb 13;20(6):064208. doi: 10.1088/0953-8984/20/6/064208. Epub 2008 Jan 24.
2
Structure of infectious prions: stabilization by domain swapping.
FASEB J. 2005 Nov;19(13):1778-82. doi: 10.1096/fj.05-4067hyp.
3
Copper(II) inhibits in vitro conversion of prion protein into amyloid fibrils.
Biochemistry. 2005 May 10;44(18):6776-87. doi: 10.1021/bi050251q.
4
The prion protein gene: identifying regulatory signals using marsupial sequence.
Gene. 2005 Apr 11;349:121-34. doi: 10.1016/j.gene.2004.11.049.
5
Effect of metal ions on de novo aggregation of full-length prion protein.
Biochem Biophys Res Commun. 2004 Aug 6;320(4):1240-6. doi: 10.1016/j.bbrc.2004.06.075.
6
Evidence for assembly of prions with left-handed beta-helices into trimers.
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8342-7. doi: 10.1073/pnas.0402254101. Epub 2004 May 21.
7
From conversion to aggregation: protofibril formation of the prion protein.
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2293-8. doi: 10.1073/pnas.0307178101.
8
Prion protein suppresses perturbation of cellular copper homeostasis under oxidative conditions.
Biochem Biophys Res Commun. 2004 Jan 23;313(4):850-5. doi: 10.1016/j.bbrc.2003.12.020.
9
The octapeptide repeats in mammalian prion protein constitute a pH-dependent folding and aggregation site.
J Mol Biol. 2003 Nov 28;334(3):477-88. doi: 10.1016/j.jmb.2003.09.048.
10
Copper chelation delays the onset of prion disease.
J Biol Chem. 2003 Nov 21;278(47):46199-202. doi: 10.1074/jbc.C300303200. Epub 2003 Sep 30.
Zotero 插件