De Marothy Minttu T, Elofsson Arne
Department of Biochemistry and Biophysics Science for Life Laboratory, Stockholm University, Solna, SE-171 21, Sweden.
Protein Sci. 2015 Jul;24(7):1057-74. doi: 10.1002/pro.2698. Epub 2015 May 30.
Cells have developed an incredible machinery to facilitate the insertion of membrane proteins into the membrane. While we have a fairly good understanding of the mechanism and determinants of membrane integration, more data is needed to understand the insertion of membrane proteins with more complex insertion and folding pathways. This review will focus on marginally hydrophobic transmembrane helices and their influence on membrane protein folding. These weakly hydrophobic transmembrane segments are by themselves not recognized by the translocon and therefore rely on local sequence context for membrane integration. How can such segments reside within the membrane? We will discuss this in the light of features found in the protein itself as well as the environment it resides in. Several characteristics in proteins have been described to influence the insertion of marginally hydrophobic helices. Additionally, the influence of biological membranes is significant. To begin with, the actual cost for having polar groups within the membrane may not be as high as expected; the presence of proteins in the membrane as well as characteristics of some amino acids may enable a transmembrane helix to harbor a charged residue. The lipid environment has also been shown to directly influence the topology as well as membrane boundaries of transmembrane helices-implying a dynamic relationship between membrane proteins and their environment.
细胞已经进化出一套令人惊叹的机制来促进膜蛋白插入膜中。虽然我们对膜整合的机制和决定因素有了相当深入的了解，但仍需要更多数据来理解具有更复杂插入和折叠途径的膜蛋白的插入过程。本综述将聚焦于疏水性较弱的跨膜螺旋及其对膜蛋白折叠的影响。这些弱疏水性跨膜片段本身无法被转运体识别，因此依赖局部序列环境进行膜整合。这样的片段如何驻留在膜内呢？我们将根据蛋白质本身以及其所处环境中的特征来探讨这一问题。已有研究描述了蛋白质中的几个特征会影响疏水性较弱螺旋的插入。此外，生物膜的影响也很显著。首先，膜内极性基团的实际成本可能不像预期的那么高；膜中蛋白质的存在以及某些氨基酸的特性可能使跨膜螺旋能够容纳一个带电荷的残基。脂质环境也已被证明会直接影响跨膜螺旋的拓扑结构以及膜边界，这意味着膜蛋白与其环境之间存在动态关系。
