The role of salt concentration and magnesium binding in HIV-1 subtype-A and subtype-B kissing loop monomer structures.
The role of salt concentration and magnesium binding in HIV-1 subtype-A and subtype-B kissing loop monomer structures.
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DOI：
10.1080/07391102.2012.706072
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发表时间：
2013
影响因子：
4.4
通讯作者：
Shapiro BA
中科院分区：
文献类型：
--
作者：
Kim T;Shapiro BA
人类免疫缺陷病毒1型（HIV-1）的亚型B单体在高盐浓度下或在镁存在下实验显示二聚化，而亚型A单体的二聚化需要镁结合在G273或G274磷酸基团上，而与盐浓度无关。我们采用显式溶剂分子动力学（MD）模拟方法研究了不同盐浓度下A和B亚型单体的构象变化，发现MD模拟结果与实验结果一致。在低盐浓度下，两种亚型的发夹环结构都发生了变形，发夹环中的碱基都转向了内侧。在高盐浓度下，B亚型单体保持发夹环形状，发夹环中的大多数碱基指出，而A亚型单体显示出严重的变形。我们还发现B亚型中的侧翼碱基稳定发夹环，而A亚型中的侧翼碱基G273引起显著变形。然而，在G273或G274磷酸基团处结合的镁离子控制了G273碱基的行为，并防止了亚型A单体的变形。我们还对这两种亚型进行了限制，以研究高盐浓度或镁结合的作用。当施加限制时，两种亚型在0 M盐浓度下保持其形状。然而，当束缚被移除时，它们显着变形。因此，我们认为，这两种亚型的二聚化需要适当的构象的单体，这是诱导适当的盐强度和镁离子结合。
The subtype-B monomers of the human immunodeficiency virus type-1 (HIV-1) have experimentally been shown to dimerize at high salt concentration or in the presence of magnesium, while the dimerization of the subtype-A monomers requires magnesium binding at the G273 or G274 phosphate groups regardless of salt concentration. We used explicit solvent molecular dynamics (MD) simulations to investigate the conformational changes in subtype-A and -B monomers in different salt concentrations, and we found that our MD simulation results are consistent with those of experiments. At low salt concentration, hairpin loop structures of both subtypes were deformed and bases in the hairpin loop were turned inside. At high salt concentrations, the subtype-B monomer maintained the hairpin loop shape and most bases in the hairpin loop pointed out, while the subtype-A monomer showed a severe deformation. We also found that the flanking bases in the subtype-B stabilize the hairpin loop, while the flanking base G273 in the subtype-A caused a significant deformation. However, a bound magnesium ion at the G273 or G274 phosphate groups controlled the behavior of the G273 base and prevented the subtype-A monomer from deformation. We also applied restraints to both subtypes to examine the role of high salt concentration or magnesium binding. While restraints were applied, both subtypes at 0 M salt concentration maintained their shapes. However, when restraints were removed, they deformed significantly. Therefore, we suggest that the dimerization of both subtypes requires the proper conformation of the monomers which is induced by the appropriate salt strength and magnesium ion binding.
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影响因子：
14.9
作者：
Kieken F;Paquet F;Brulé F;Paoletti J;Lancelot G
通讯作者：
Lancelot G
影响因子：
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作者：
Chworos, A;Severcan, I;Jaeger, L
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Jaeger, L
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2
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Hansma, HG;Oroudjev, E;Jaeger, L
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Jaeger, L
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JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
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KLEIN, ML
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG