Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, California 90095, USA.
J Am Chem Soc. 2011 Jul 27;133(29):11389-98. doi: 10.1021/ja204524c. Epub 2011 Jul 5.
Membrane proteins have evolved to fold and function in a lipid bilayer, so it is generally assumed that their stability should be optimized in a natural membrane environment. Yet optimal stability is not always in accord with optimization of function, so evolutionary pressure, occurring in a complex membrane environment, may favor marginal stability. Here, we find that the transmembrane helix dimer, glycophorin A (GpATM), is actually much less stable in the heterogeneous environment of a natural membrane than it is in model membranes and even common detergents. The primary destabilizing factors are electrostatic interactions between charged lipids and charged GpATM side chains, and nonspecific competition from other membrane proteins. These effects overwhelm stabilizing contributions from lateral packing pressure and excluded volume. Our work illustrates how evolution can employ membrane composition to modulate protein stability.
膜蛋白在脂质双层中折叠和发挥功能，因此通常认为它们的稳定性应该在自然膜环境中得到优化。然而，最佳稳定性并不总是与功能优化一致，因此，在复杂的膜环境中，进化压力可能有利于边缘稳定性。在这里，我们发现跨膜螺旋二聚体糖蛋白 A（GpATM）在天然膜的非均相环境中的稳定性实际上比在模型膜甚至常见的去污剂中要低得多。主要的去稳定因素是带电荷的脂质与带电荷的 GpATM 侧链之间的静电相互作用，以及来自其他膜蛋白的非特异性竞争。这些效应压倒了来自侧向包装压力和排除体积的稳定贡献。我们的工作说明了进化如何利用膜成分来调节蛋白质稳定性。
