Biozentrum, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland.
Protein J. 2019 Jun;38(3):306-316. doi: 10.1007/s10930-019-09827-6.
Most membrane proteins are composed of hydrophobic α-helical transmembrane segments and are integrated into the lipid bilayer of the endoplasmic reticulum by the highly conserved Sec61 translocon. With respect to the integration mechanism, three types of transmembrane segments can be distinguished-the signal, the stop-transfer sequence, and the re-integration sequence-which in linear succession can account for all kinds of membrane protein topologies. The transmembrane orientation of the initial signal and to a weaker extent also of downstream transmembrane segments is affected by charged flanking residues according to the so-called positive-inside rule. The main driving force for transmembrane integration is hydrophobicity. Systematic analysis suggested thermodynamic equilibration of each peptide segment in the translocon with the membrane as the underlying mechanism. However, there is evidence that integration is not entirely sequence-autonomous, but depends also on the sequence context, from very closely spaced transmembrane segments to the folding state and properties of neighboring sequences. Topogenesis is even influenced by accessory proteins that appear to act as intramembrane chaperones.
大多数膜蛋白由疏水性 α 螺旋跨膜片段组成，并通过高度保守的 Sec61 转运蛋白整合到内质网膜的脂质双层中。就整合机制而言，可以区分三种类型的跨膜片段 - 信号序列、停止转移序列和重新整合序列 - 它们按线性顺序可以解释所有类型的膜蛋白拓扑结构。初始信号以及在较小程度上下游跨膜片段的跨膜取向受带电侧翼残基的影响，根据所谓的正内部规则。跨膜整合的主要驱动力是疏水性。系统分析表明，每个肽段与膜之间的热力学平衡是转运蛋白的潜在机制。然而，有证据表明整合并非完全是序列自主的，还取决于序列上下文，从非常紧密间隔的跨膜片段到折叠状态和相邻序列的性质。拓扑发生甚至受到辅助蛋白的影响，这些蛋白似乎作为跨膜伴侣蛋白发挥作用。
