How lipids affect the energetics of co-translational alpha helical membrane protein folding.
How lipids affect the energetics of co-translational alpha helical membrane protein folding.
复制标题
DOI：
10.1042/bst20201063
复制
发表时间：
2022-02-28
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
膜蛋白需要精确折叠才能正确发挥功能，错误折叠可能会导致疾病。蛋白质存在于疏水性脂质膜内，并且必须插入膜中并正确折叠，通常是在它们被核糖体翻译的同时。有利的和不利的自由能的贡献是目前在整个插入和折叠的每个阶段。将肽键转移到疏水膜内部的不利能量成本通过将疏水跨膜α-螺旋分配到膜中的有利疏水效应来补偿。天然膜由许多不同类型的脂质组成，但这些不同的脂质如何影响折叠和相关的自由能还不清楚。已知改变双层中的脂质会影响跨膜螺旋插入膜中的概率，并且脂质也会影响蛋白质稳定性并可促进成功折叠。这篇综述将总结与α螺旋膜蛋白的插入和折叠相关的自由能贡献，以及脂质如何使这些过程或多或少有利。我们还将讨论这项工作的影响，在α螺旋膜蛋白的共翻译折叠过程中的自由能景观。
Membrane proteins need to fold with precision in order to function correctly, with misfolding potentially leading to disease. The proteins reside within a hydrophobic lipid membrane and must insert into the membrane and fold correctly, generally whilst they are being translated by the ribosome. Favourable and unfavourable free energy contributions are present throughout each stage of insertion and folding. The unfavourable energy cost of transferring peptide bonds into the hydrophobic membrane interior is compensated for by the favourable hydrophobic effect of partitioning a hydrophobic transmembrane alpha-helix into the membrane. Native membranes are composed of many different types of lipids, but how these different lipids influence folding and the associated free energies is not well understood. Altering the lipids in the bilayer is known to affect the probability of transmembrane helix insertion into the membrane, and lipids also affect protein stability and can promote successful folding. This review will summarise the free energy contributions associated with insertion and folding of alpha helical membrane proteins, as well as how lipids can make these processes more or less favourable. We will also discuss the implications of this work for the free energy landscape during the co-translational folding of alpha helical membrane proteins.