據(jù)一篇發(fā)表于9月28日PLoS ONE雜志網絡版的研究報告,，多倫多大學的研究人員發(fā)現(xiàn)了阮病毒基因的進化祖先,，該研究或許能給科學家對朊蛋白的致病機制有一個全新的認識。
朊病毒能導致多種神經退行性疾病,，如克雅氏病(CJD),，牛海綿狀腦病(BSE) 慢性消耗病(CWD)等。研究人員Gerold Schmitt-Ulms等人對朊蛋白家族各個成員的生理功能進行研究,。課題組的分析表明朊病毒基因是由古老的金屬離子轉運體ZIP家族進化而來,。ZIP蛋白家族主要負責細胞膜內外鋅離子或其他金屬離子的轉運工作。
研究人員發(fā)現(xiàn)兩種金屬轉運體ZIP6和ZIP10與哺乳動物中朊蛋白的生理功能非常接近,。ZIP6和ZIP10在腦部組織中表達水平很高,，并且研究人員發(fā)現(xiàn),，朊蛋白和ZIP蛋白含有大量相似的氨基酸序列和高度相似的空間結構,。
ZIP家族和朊蛋白之間的這種聯(lián)系或將為研究人員研究朊蛋白提供全新的視角。（生物谷bioon.com）
生物谷推薦原始出處：
PLoS ONE 4(9): e7208. doi:10.1371/journal.pone.0007208
Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters
Gerold Schmitt-Ulms1,2*, Sepehr Ehsani1,2, Joel C. Watts1,2,3, David Westaway5, Holger Wille3,4
1 Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada, 2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, 3 Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, United States of America, 4 Department of Neurology, University of California San Francisco, San Francisco, California, United States of America, 5 Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada
In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transporters of the ZIP family, ZIP6 and ZIP10, to mammalian prion proteins in vivo. A subsequent bioinformatic analysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species place the split from the ZIP-like ancestor gene at the base of the chordate lineage. This relationship explains structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The phylogenetic and spatial connection to ZIP proteins is expected to open new avenues of research to elucidate the biology of the prion protein in health and disease.
