Fletcher T G, Keire D A
Beckman Research Institute, City of Hope, Duarte, California 91010-0269, USA.
Protein Sci. 1997 Mar;6(3):666-75. doi: 10.1002/pro.5560060316.
The neurotoxicity of beta-amyloid protein (beta AP) fragments may be a result of their solution conformation, which is very sensitive to solution conditions. In this work we describe NMR and CD studies of the conformation of beta AP(12-28) in lipid (micelle) environments as a function of pH and lipid type. The interaction of beta AP(12-28) with zwitterionic dodecylphosphocholine (DPC) micelles is weak and alters the conformation when compared to water solution alone. By contrast, the interaction of the peptide with anionic sodium dodecylsulfate (SDS) micelles is strong: beta AP(12-28) is mostly bound, is alpha-helical from K16 to V24, and aggregates slowly. The pH-dependent conformation changes of beta AP(12-28) in solution occur in the pH range at which the side-chain groups of E22, D23, H13, and H14 are deprotonated (pKas ca. 4 and 6.5); the interaction of beta AP(12-28) with SDS micelles alters the pH-dependent conformational transitions of the peptide whereas the weak interaction with DPC micelles causes little change.
β-淀粉样蛋白（βAP）片段的神经毒性可能是其溶液构象所致，该构象对溶液条件非常敏感。在这项工作中，我们描述了βAP（12 - 28）在脂质（胶束）环境中的构象的核磁共振（NMR）和圆二色（CD）研究，作为pH值和脂质类型的函数。βAP（12 - 28）与两性离子十二烷基磷酸胆碱（DPC）胶束的相互作用较弱，与单独的水溶液相比会改变构象。相比之下，该肽与阴离子十二烷基硫酸钠（SDS）胶束的相互作用较强：βAP（12 - 28）大多被结合，从K16到V24呈α螺旋结构，且聚集缓慢。βAP（12 - 28）在溶液中的pH依赖性构象变化发生在E22、D23、H13和H14的侧链基团去质子化的pH范围内（pKa约为4和6.5）；βAP（12 - 28）与SDS胶束的相互作用改变了该肽的pH依赖性构象转变，而与DPC胶束的弱相互作用几乎没有引起变化。
