Walsh Patrick, Yau Jason, Simonetti Karen, Sharpe Simon
Molecular Structure and Function Program, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
Biochemistry. 2009 Jun 30;48(25):5779-81. doi: 10.1021/bi9007319.
The formation of nonfibrillar oligomers has been proposed to be a common element of the aggregation pathway of amyloid peptides. Here we describe the first detailed investigation of the morphology and secondary structure of stable oligomers formed by a peptide comprising residues 106-126 of the human prion protein (PrP). These oligomers have an apparent hydrodynamic radius of approximately 30 nm and are more membrane-active than monomeric or fibrillar PrP(106-126). Circular dichroism and solid state NMR data support formation of an extended beta-strand by the hydrophobic core of PrP(106-126), while negative thioflavin-T binding implies an absence of cross-beta structure in nonfibrillar oligomers.
非纤维状寡聚体的形成被认为是淀粉样肽聚集途径的一个共同要素。在此，我们描述了对由人朊病毒蛋白（PrP）106 - 126位残基组成的肽形成的稳定寡聚体的形态和二级结构的首次详细研究。这些寡聚体的表观流体动力学半径约为30 nm，且比单体或纤维状PrP(106 - 126)具有更强的膜活性。圆二色性和固态核磁共振数据支持PrP(106 - 126)的疏水核心形成延伸的β - 链，而硫黄素 - T结合阴性表明非纤维状寡聚体中不存在交叉β结构。
