3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

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• 作者：P.X. Cui ; F.L. Lian ; Y. Wang ; Yi Wen ; W.S. Chu ; H.F. Zhao ; S. Zhang ; J. Li ; D.H. Lin ; Z.Y. Wu
• 关键词：PrP ; prion-related protein ; TSE ; transmissible spongiform encephalopathies ; PrPC ; cellular prion protein ; PrPSc ; scrapie prion protein ; RaPrPC ; rabbit prion protein ; XANES ; X-ray absorption near-edge structure ; EXAFS ; extended X-ray absorption fine structure ; MS ; multiple scattering ; MXAN ; Minuit XANES ; a software package to reconstruct 3D structures from XANES spectra ; XAS ; X-ray absorption spectra ; MT ; muffin-tin ; FT ; Fourier transform
• 刊名：Radiation Physics and Chemistry
• 出版年：February, 2014
• 年：2014
• 卷：95
• 期：Complete
• 页码：69-72
• 全文大小：684 K

文摘

Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrP^C) to the post-translationally modified form (PrP^Sc) is thought to be relevant to Cu²⁺ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrP^C) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.