Structural determinants of transmembrane β-barrels
Structural determinants of transmembrane β-barrels
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DOI：
10.1021/ct050055x
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发表时间：
2005-07-01
影响因子：
5.5
通讯作者：
Lazaridis, T
中科院分区：
文献类型：
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作者：
Lazaridis, T
基于β -桶状膜蛋白序列的识别比基于α -螺旋状膜蛋白的识别更具挑战性。这一目标可能受益于更好地理解跨膜-桶结构的物理决定因素。为此，我们首先扩展了IMM1隐式膜模型，使其能够对具有内部水孔的膜蛋白进行建模。新模型（IMM1-pore）给出了三种不同大小的β -桶膜蛋白的稳定分子动力学轨迹和合理大小的负水-膜传递能。它还能区分一对10链和12链跨膜β -桶的正确折叠。然后我们考虑了一对β -桶蛋白：OmpA，它是一种膜β -桶，外部有疏水残基，内部有极性残基；视黄醇结合蛋白，它是一种水溶性蛋白，外部有极性残基，内部有疏水残基。通过将一个序列串到另一个序列的结构上，我们为每个序列生成两对结构，一个是原生结构，另一个是诱饵结构，并评估它们的能量。能量函数区分正确的结构。通过将能量分解为残基贡献，我们检查每个序列的哪些特征使其折叠成一个或另一个结构。研究发现，对于OmpA序列，最大的稳定性贡献来自于筒体内部极性残基之间的相互作用。阻止视黄醇结合蛋白序列采用跨膜折叠的主要因素是在假定的跨膜β链边缘存在极性/带电残基以及不太有利的内部极性残基相互作用。这些结果有助于设计简化的评分函数，用于跨膜β -桶的褶皱识别和结构预测。
The recognition of beta-barrel membrane proteins based on their sequence is more challenging than the recognition of alpha-helical membrane proteins. This goal could benefit from a better understanding of the physical determinants of transmembrane beta-barrel structure. To that end, we first extend the IMM1 implicit membrane model in a way that allows the modeling of membrane proteins with an internal aqueous pore. The new model (IMM1-pore) gives stable molecular dynamics trajectories for three beta-barrel membrane proteins of different sizes and negative water-to-membrane transfer energies of reasonable magnitude. It also discriminates the correct fold for a pair of 10-stranded and 12-stranded transmembrane beta-barrels. We then consider a pair of beta-barrel proteins: OmpA, which is a membrane beta-barrel with hydrophobic residues on the exterior and polar residues in the interior, and retinol binding protein, which is a water soluble protein with polar residues on the exterior and hydrophobic residues in the interior. By threading the sequence of one onto the structure of the other we make two pairs of structures for each sequence, one native and the other a decoy, and evaluate their energy. The energy function discriminates the correct structure. By decomposing the energy into residue contributions we examine which features of each sequence make it fold into one or the other structure. It is found that for the OmpA sequence the largest contribution to stability comes from interactions between polar residues in the interior of the barrel. The major factor that prevents the retinol binding protein sequence from adopting a transmembrane fold is the presence of polar/charged residues at the edges of the putative transmembrane beta-strands as well as the less favorable interior polar residue interactions. These results could help design simplified scoring functions for fold recognition and structure prediction of transmembrane beta-barrels.