Theoretically determined three-dimensional structures for amphipathic segments of the HIV-1 gp41 envelope protein.
Theoretically determined three-dimensional structures for amphipathic segments of the HIV-1 gp41 envelope protein.
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理论上确定了 HIV-1 gp41 包膜蛋白两亲片段的三维结构。
DOI：
10.1089/aid.1989.5.7
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发表时间：
1989
影响因子：
1.5
通讯作者：
Carson,FW
中科院分区：
文献类型：
--
作者：
Venable,RM;Pastor,RW;Brooks,BR;Carson,FW
利用结构预测技术，结合能量最小化和分子动力学模拟，建立了艾滋病跨膜蛋白gp 41 C端两个片段的三维计算机模型。HIV-1 HXB 2株的gp 41（772-790）和gp 41（828-848）区域作为α-螺旋显示出非常高的疏水矩最大值，并且当处于反平行构象时显示出电荷互补性，这意味着它们可以彼此结合并与膜缔合。这一假设的可行性进行了测试，在一系列的计算机模拟这些肽，延长了几个残基，包括额外的电荷配对。从770-794和824-856段的反平行α螺旋形式的试验结构开始，系统的轴向旋转和位移被用来产生替代的初始状态。α-螺旋扭转约束的分子动力学模拟产生了几个近似圆柱形的二聚体结构，这些结构通过大量的盐键和其他氢键高度稳定。这表明，这两个区域可能以反平行的方式相互折叠，在第770-856位残基的三级结构中形成一个环，该环由膜相关的两亲性α-螺旋闭合，带电侧彼此面对。我们推测，这种结构可以聚集形成通道或以其他方式破坏膜的稳定性，从而有助于gp 120-gp 41复合物的致细胞病变效应。
Three-dimensional computer models for two segments of the C terminus of gp41, the transmembrane AIDS envelope protein, which may form amphipathic α-helices, have been generated using structure prediction techniques combined with energy minimization and molecular dynamics simulations. Regions gp41(772–790) and gp41(828–848) of the HXB2 strain of HIV-1 display extraordinarily high hydrophobic moment maxima as α-helices and when in an antiparallel conformation exhibit charge complementarity, implying that they may bind with each other and associate with the membrane. The feasibility of this hypothesis was tested in a series of computer simulations of these peptides, extended by several residues to include additional charge pairing. Beginning with a trial structure in the form of antiparallel α-helices of segments 770–794 and 824–856, systematic axial rotations and displacements were used to generate alternative initial states. Molecular dynamics simulations with α-helical torsional restraints yielded several approximately cylindrical dimeric structures highly stabilized by numerous salt links and other hydrogen bonds. This suggests that these two regions may fold back on each other in antiparallel fashion to form a loop in the tertiary structure over residues 770–856, with the loop closed by membrane-associated amphipathic α-helices with charged sides facing each other. We speculate that such structures could aggregate to form channels or otherwise destabilize the membrane, thereby contributing to the cytopathic effects of the gp120-gp41 complex.