The role of lipids in mechanosensation.
The role of lipids in mechanosensation.
复制标题
DOI：
10.1038/nsmb.3120
复制
发表时间：
2015-12
影响因子：
16.8
通讯作者：
Naismith JH
中科院分区：
文献类型：
--
作者：
Pliotas C;Dahl AC;Rasmussen T;Mahendran KR;Smith TK;Marius P;Gault J;Banda T;Rasmussen A;Miller S;Robinson CV;Bayley H;Sansom MS;Booth IR;Naismith JH
蛋白质感知膜张力的能力在生物学中普遍存在。大肠杆菌 MscS 的高分辨率结构（小电导通道）可识别由跨膜螺旋 (TM) 形成的口袋内的烷基链。纯化的 MscS 含有大肠杆菌脂质，荧光猝灭表明磷脂酰基链在双层和 TM 口袋之间交换。分子动力学和生物物理分析表明，当通道打开时，袋的体积以及其中的脂酰基链的数量减少。每个头基团具有一个酰基链的磷脂（溶血脂）会取代 MscS 口袋中的正常磷脂（两个酰基链）并触发通道开放。我们认为这些口袋中酰基链交错的程度决定了 MScS 的构象。当相互交叉受到增加的膜张力或溶血脂的干扰时，关闭状态变得不稳定并且通道门。
The ability of proteins to sense membrane tension is pervasive in biology. A higher resolution structure of E. coli MscS, the channel of small conductance, identifies alkyl chains inside pockets formed by the transmembrane helices (TMs). Purified MscS contains E. coli lipids and fluorescence quenching demonstrates that phospholipid acyl chains exchange between bilayer and TM pockets. Molecular dynamics and biophysical analyses show that the volume of the pockets and thus the number of lipid acyl chain within them decreases upon channel opening. Phospholipids with one acyl chain per head group (lysolipids) displace normal phospholipids (two acyl chains) from MscS pockets and trigger channel opening. We propose the extent of acyl chain interdigitation in these pockets determines the conformation of MscS. Where interdigitation is perturbed by increased membrane tension or by lysolipids, the closed state becomes unstable and the channel gates.