Department of Chemistry, University of California, Berkeley, California, USA.
Biophys J. 2012 Sep 19;103(6):1227-35. doi: 10.1016/j.bpj.2012.08.035.
The packing structures of transmembrane helices are traditionally attributed to patterns in residues along the contact surface. In this view, besides keeping the helices confined in the membrane, the bilayer has only a minor effect on the helices structure. Here, we use two different approaches to show that the lipid environment has a crucial effect in determining the cross-angle distribution of packed helices. We analyzed structural data of a membrane proteins database. We show that the distribution of cross angles of helix pairs in this database is statistically indistinguishable from the cross-angle distribution of two noninteracting helices imbedded in the membrane. These results suggest that the cross angle is, to a large extent, determined by the tilt angle of the individual helices. We test this hypothesis using molecular simulations of a coarse-grained model that contains no specific residue interactions. These simulations reproduce the same cross-angle distribution as found in the database. As the tilt angle of a helix is dominated by hydrophobic mismatch between the protein and surrounding lipids, our results indicate that hydrophobic mismatch is the dominant factor guiding the transmembrane helix packing. Other short-range forces might then fine-tune the structure to its final configuration.
跨膜螺旋的包装结构传统上归因于接触表面上残基的模式。从这个角度来看，除了将螺旋限制在膜内，双层膜对螺旋结构只有很小的影响。在这里，我们使用两种不同的方法来表明脂质环境对确定包装螺旋的交叉角分布有至关重要的影响。我们分析了膜蛋白数据库的结构数据。我们表明，该数据库中螺旋对的交叉角分布与嵌入膜中的两个非相互作用螺旋的交叉角分布在统计学上无法区分。这些结果表明，交叉角在很大程度上取决于单个螺旋的倾斜角。我们使用包含无特定残基相互作用的粗粒度模型的分子模拟来检验这一假设。这些模拟重现了数据库中发现的相同的交叉角分布。由于螺旋的倾斜角主要由蛋白质和周围脂质之间的疏水性失配决定，我们的结果表明疏水性失配是指导跨膜螺旋包装的主要因素。然后，其他短程力可以将结构微调为最终构型。
