The importance of the membrane interface as the reference state for membrane protein stability.
The importance of the membrane interface as the reference state for membrane protein stability.
复制标题
膜界面作为膜蛋白稳定性参考状态的重要性。
DOI：
10.1016/j.bbamem.2018.09.012
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Ulmschneider MB
中科院分区：
文献类型：
--
作者：
Ulmschneider JP;Smith JC;White SH;Ulmschneider MB
新生多肽链插入脂双层膜和膜蛋白的稳定性关键取决于多肽的平衡分配。为此，必须了解氨基酸残基的完整序列转移到双层中，而不是单个氨基酸。早期的研究表明，最有可能的参考状态分区非常疏水的序列是膜界面。我们使用µ s尺度模拟来计算两个疏水载体序列的界面-跨膜分配自由能ΔGS→TM，以估计所有20个氨基酸残基在与分配疏水肽中心结合时的插入自由能。我们的研究结果表明，以前的单残基尺度可能高估了多肽的分配自由能。ΔGS→TM与实验全肽转位子插入数据的相关性很高，表明膜界面在基于转位子的插入中起重要作用。载体序列的选择极大地调节了每个单残基突变对整体分配自由能的贡献。我们的研究结果表明，量化所观察到的全肽分配平衡，这是膜界面和跨膜插入，而不是结合个人的水膜氨基酸转移自由能的重要性。准确测定基因组序列中的膜包埋片段，并从氨基酸序列预测膜蛋白结构，关键取决于精确定量的多肽分配到脂质双层。早期的研究表明，最有可能的参考状态分配非常疏水的序列是膜界面，即相关的平衡是界面跨膜分配。本文描述了第一个全肽界面跨膜分配自由能尺度的疏水载体序列的所有20个氨基酸残基。与实验的全肽translocon插入数据的相关性是高的，这表明膜界面在translocon为基础的插入的重要作用。
The insertion of nascent polypeptide chains into lipid bilayer membranes and the stability of membrane proteins crucially depend on the equilibrium partitioning of polypeptides. For this, the transfer of full sequences of amino-acid residues into the bilayer, rather than individual amino acids, must be understood. Earlier studies have revealed that the most likely reference state for partitioning very hydrophobic sequences is the membrane interface. We have used µs-scale simulations to calculate the interface-to-transmembrane partitioning free energies ΔGS→TM for two hydrophobic carrier sequences in order to estimate the insertion free energy for all 20 amino acid residues when bonded to the center of a partitioning hydrophobic peptide. Our results show that prior single-residue scales likely overestimate the partitioning free energies of polypeptides. The correlation of ΔGS→TM with experimental full-peptide translocon insertion data is high, suggesting an important role for the membrane interface in translocon-based insertion. The choice of carrier sequence greatly modulates the contribution of each single-residue mutation to the overall partitioning free energy. Our results demonstrate the importance of quantifying the observed full-peptide partitioning equilibrium, which is between membrane interface and transmembrane inserted, rather than combining individual water-to-membrane amino acid transfer free energies. The accurate determination of membrane embedded segments in genome sequences, and prediction of membrane protein structure from amino-acid sequence depend crucially on the precise quantification of polypeptide partitioning into lipid bilayers. Earlier studies have revealed that most likely reference state for partitioning very hydrophobic sequences is the membrane interface, i.e. the relevant equilibrium is that of interface-to-transmembrane partitioning. This paper describes the first full-peptide interface-to-transmembrane partitioning free energy scale for hydrophobic carrier sequences for all 20 amino acid residues. The correlation with experimental full-peptide translocon insertion data is high, suggesting an important role for the membrane interface in translocon-based insertion.
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