Department of Chemistry, 418 Seeley G. Mudd Building, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089-1062, USA.
Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17598-603. doi: 10.1073/pnas.1012207107. Epub 2010 Sep 27.
The understanding of the mechanism of insertion of transmembrane (TM) helixes through the translocon presents a major open challenge. Although the experimental information about the partition of the inserted helices between the membrane and the solution contains crucial information about this process, it is not clear how to extract this information. In particular, it is not clear how to rationalize the small apparent insertion energy, ΔG(app), of an ionized residue in the center of a TM helix. Here we explore the nature of the insertion energies, asking what should be the value of these parameters if their measurements represent equilibrium conditions. This is done using a coarse-grained model with advanced electrostatic treatment. Estimating the energetics of ionized arginine of a TM helix in the presence of neighboring helixes or the translocon provides a rationale for the observed ΔG(app) of ionized residues. It is concluded that the apparent insertion free energy of TM with charged residues reflects probably more than just the free energy of moving the isolate single helix from water into the membrane. The present approach should be effective not only in exploring the mechanism of the operation of the translocon but also for studies of other membrane proteins.
跨膜（TM）螺旋插入机制的理解提出了一个主要的开放性挑战。尽管关于插入螺旋在膜和溶液之间分配的实验信息包含了关于这个过程的关键信息，但目前还不清楚如何提取这些信息。特别是，如何合理化 TM 螺旋中心离子化残基的小表观插入能 ΔG(app) 尚不清楚。在这里，我们探讨了插入能的性质，询问如果它们的测量代表平衡条件，这些参数应该具有什么值。这是使用具有先进静电处理的粗粒模型来完成的。在存在相邻螺旋或跨膜的情况下，估算 TM 螺旋中离子化精氨酸的能量学为观察到的离子化残基的 ΔG(app) 提供了合理的解释。可以得出结论，带电荷残基的 TM 的表观插入自由能可能反映的不仅仅是将孤立的单链从水中移动到膜中的自由能。这种方法不仅应该对探索跨膜的作用机制有效，而且对其他膜蛋白的研究也有效。
