Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization.
Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization.
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DOI：
10.1021/bi800678t
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发表时间：
2008-09
期刊：
影响因子：
2.9
通讯作者：
Emi Psachoulia;P. Fowler;P. Bond;M. Sansom
中科院分区：
文献类型：
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作者：
Emi Psachoulia;P. Fowler;P. Bond;M. Sansom
跨膜（TM）螺旋的寡聚化是膜蛋白折叠的关键阶段。血型糖蛋白A（GpA）是该过程的有据可查的检测系统。粗粒分子动力学（CG-MD）使我们能够模拟TM螺旋自组装成二聚体，野生型（WT）和突变型GpA序列。对于WT序列，二聚体快速形成，并在所有模拟中保持稳定。所得的二聚体表现出右手交叉和相同的螺旋间的NMR结构中的接触。破坏性突变体的模拟显示二聚体不太稳定，与实验数据一致的DeltaDelta G二聚化的值。破坏性突变体的二聚体相对于WT是扭曲的，并且显示出它们的螺旋的左手交叉。因此，CG-MD可用于探索TM螺旋的相互作用，这是膜蛋白折叠的重要阶段。特别是，CG-MD已被证明是足够敏感的检测突变引入的中断。未来通过原子模拟对这种模型的改进将使多尺度方法能够预测膜蛋白的折叠。
Oligomerization of transmembrane (TM) helices is a key stage in the folding of membrane proteins. Glycophorin A (GpA) is a well-documented test system for this process. Coarse-grained molecular dynamics (CG-MD) allows us to simulate the self-assembly of TM helices into dimers, for both wild-type (WT) and mutant GpA sequences. For the WT sequences, dimers formed rapidly and remained stable in all simulations. The resultant dimers exhibited right-handed crossing and the same interhelix contacts as in NMR structures. Simulations of disruptive mutants revealed the dimers were less stable, with values of DeltaDelta G dimerization consistent with experimental data. The dimers of disruptive mutants were distorted relative to the WT and showed left-handed crossing of their helices. CG-MD can therefore be used to explore the interactions of TM helices, an important stage in the folding of membrane proteins. In particular, CG-MD has been shown to be sensitive enough to detect disruptions introduced by mutation. Future refinement of such models via atomistic simulations will enable a multiscale approach to predict the folding of membrane proteins.