Unveiling the Role of Histidine and Tyrosine Residues on the Conformation of the Avian Prion Hexarepeat Domain

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• 作者：Adriana Pietropaolo ; Luca Muccioli ; Claudio Zannoni ; Diego La Mendola ; Giuseppe Maccarrone ; Giuseppe Pappalardo ; Enrico Rizzarelli
• 刊名：Journal of Physical Chemistry B
• 出版年：2008
• 出版时间：April 24, 2008
• 年：2008
• 卷：112
• 期：16
• 页码：5182 - 5188
• 全文大小：385K
• 年卷期：v.112,no.16(April 24, 2008)
• ISSN：1520-5207

文摘

The prion protein (PrP<SUP>C) is a glycoprotein that in mammals, differently from avians, can lead to prion diseases,by misfolding into a ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-sheet-rich pathogenic isoform (PrP^Sc). Mammal and avian proteins show differentN-terminal tandem repeats: PHGGGWGQ and PHNPGY, both containing histidine, whereas tyrosine isincluded only in the primary sequence of the avian protein. Here, by means of potentiometric, circular dichroism(CD), and molecular dynamics (MD) studies at different pH values, we have investigated the conformationof the avian tetrahexarepeat (PHNPGY)₄ (TetraHexaPY) with both N- and C-termini blocked by acetylationand amidation, respectively. We have found, also with the help of a recently proposed protein chirality indicator(Pietropaolo, A.; Muccioli, L.; Berardi, R.; Zannoni, C. Proteins 2008, 70, 667-677), a conformationaldependence on the protonation states of histidine and tyrosine residues: the turn formation is pH driven, andat physiological pH a pivotal role is played by the tyrosine OH groups which give rise to a very compact bentstructure of backbone upon forming a hydrogen-bond network.