The role of electrostatic interactions in the regulation of the membrane association of G protein βγ heterodimers
The role of electrostatic interactions in the regulation of the membrane association of G protein βγ heterodimers
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DOI：
10.1074/jbc.m101784200
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发表时间：
2001-11-30
影响因子：
4.8
通讯作者：
Honig, B
中科院分区：
文献类型：
--
作者：
Murray, D;McLaughlin, S;Honig, B
在本文中，我们报告的transducin（G（t））β γ异二聚体（G（t）β γ）和磷脂膜之间的静电相互作用的计算。虽然G（t）β γ的膜缔合主要是由于疏水性渗透到与γ亚基连接的法尼基链的膜内部，但结构研究表明，在β亚基表面上，在从G（t）α亚基解离后暴露的法尼基化位点周围存在显著的碱性残基补丁。此外，产生G（t）β γ从膜上解离的葡糖蛋白直接与G（t）β γ相互作用，并将一簇酸性残基引入该区域。的计算，这是基于有限差分泊松-玻尔兹曼方法，占一些实验观察，并建议带电残基介导蛋白质-膜相互作用中发挥作用。具体而言，计算预测如下。1)尽管G（t）β γ具有大的净负电荷（-12），但有利的静电相互作用由于法呢基基团而将膜分配增强了一个数量级。2)这种静电吸引定位G（t）β γ，使得参与介导G（t）β γ与其膜结合效应物相互作用的残基靠近膜表面。3)葡糖蛋白与G（t）β γ的结合使G（t）β γ的膜分配减少了一个数量级。4)降低溶液的离子强度将静电吸引力转化为排斥力。序列分析和同源性模型的建立表明，我们的结论可以推广到其他G β γ和β-ducin亚型以及。
In this paper we report calculations of electrostatic interactions between the transducin (G(t)) beta gamma heterodimer (G(t)beta gamma) and phospholipid membranes. Although membrane association of G(t)beta gamma is due primarily to the hydrophobic penetration into the membrane interior of a farnesyl chain attached to the gamma subunit, structural studies have revealed that there is a prominent patch of basic residues on the surface of the beta subunit surrounding the site of farnesylation that is exposed upon dissociation from the G(t)alpha subunit. Moreover, phosducin, which produces dissociation of G(t)beta gamma from membranes, interacts directly with G(t)beta gamma and introduces a cluster of acidic residues into this region. The calculations, which are based on the finite difference Poisson-Boltzmann method, account for a number of experimental observations and suggest that charged residues play a role in mediating protein-membrane interactions. Specifically, the calculations predict the following. 1) Favorable electrostatic interactions enhance the membrane partitioning due to the farnesyl group by an order of magnitude although G(t)beta gamma has a large net negative charge (-12). 2) This electrostatic attraction positions G(t)beta gamma so that residues implicated in mediating the interaction of G(t)beta gamma with its membrane-bound effectors are close to the membrane surface. 3) The binding of phosducin to G(t)beta gamma diminishes the membrane partitioning of G(t)beta gamma by an order of magnitude. 4) Lowering the ionic strength of the solution converts the electrostatic attraction into a repulsion. Sequence analysis and homology model building suggest that our conclusions may be generalized to other G beta gamma and phosducin isoforms as well.