Homans S W, Edge C J, Ferguson M A, Dwek R A, Rademacher T W
Department of Biochemistry, Oxford University, England.
Biochemistry. 1989 Apr 4;28(7):2881-7. doi: 10.1021/bi00433a020.
The average solution conformation of the glycosylphosphatidylinositol (GPI) membrane anchor of Trypanosoma brucei variant surface glycoprotein (VSG) has been determined by using a combination of two-dimensional 1H-1H NMR methods together with molecular orbital calculations and restrained molecular dynamics simulations. This allows the generation of a model to describe the orientation of the glycan with respect to the membrane. This shows that the glycan exists in an extended configuration along the plane of the membrane and spans an area of 600 A2, which is similar to the cross-sectional area of a monomeric N-terminal VSG domain. Taken together, these observations suggest a possible space-filling role for the GPI anchor that may maintain the integrity of the VSG coat. The potential importance of the GPI glycan as a chemotherapeutic target is discussed in light of these observations.
通过结合二维¹H-¹H NMR方法、分子轨道计算和受限分子动力学模拟，确定了布氏锥虫可变表面糖蛋白（VSG）的糖基磷脂酰肌醇（GPI）膜锚的平均溶液构象。这使得能够生成一个模型来描述聚糖相对于膜的取向。结果表明，聚糖沿膜平面以伸展构型存在，跨度为600 Ų，这与单体N端VSG结构域的横截面积相似。综合这些观察结果表明，GPI锚可能具有空间填充作用，从而维持VSG外壳的完整性。根据这些观察结果，讨论了GPI聚糖作为化疗靶点的潜在重要性。
