Conformation and orientation of branched acyl chains responsible for the physical stability of diphytanoylphosphatidylcholine.
Conformation and orientation of branched acyl chains responsible for the physical stability of diphytanoylphosphatidylcholine.
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DOI：
10.1021/acs.biochem.0c00589
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发表时间：
2020-09
期刊：
影响因子：
2.9
通讯作者：
H. Tsuchikawa;T. Ono;Masaki Yamagami;Yuichi Umegawa;W. Shinoda;M. Murata
中科院分区：
文献类型：
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作者：
H. Tsuchikawa;T. Ono;Masaki Yamagami;Yuichi Umegawa;W. Shinoda;M. Murata
二植烷酰磷脂酰胆碱（DPhPC）是一种合成磷脂，其中两个甲基分支的酰基链被引入甘油部分，模拟真核生物和真细菌来源的磷脂。DPhPC的脂质双层再现了古细菌膜中甲基分支脂质的出色物理性质。DPhPC通常用作生物物理实验中的基础脂质，特别是用于记录离子通道电流。然而，脂质分子诱导其有用的物理性质的动力学仍然不清楚。在这项研究中，我们研究了构象和取向的甲基支链的酰基链的DPhPC在膜中使用2 H NMR测量的合成脂质具有高的立体化学纯度和分子动力学（MD）模拟。氘标记的3 '，3'-CD 3，D-DPhPC（2）和7 '，7'-CD 3，D-DPhPC（3）在2 H NMR光谱中显示出特征性的四极分裂宽度，这对应于古细菌脂质PGP-Me报告的弯曲取向（Yamagami et al. Biochemistry 2019，58，3869-3879）。然而，MD模拟，再现了2 H NMR的结果，揭示了未知的功能，DPhPC在膜中; DPhPC具有链特异性的平均取向，其中两个弯曲的取向与向上和向下的甲基基团发生在C3和C7的位置的sn-1和sn-2链的DPhPC，分别。这些MD和NMR的结果表明，这两个弯曲的取向定义的平均取向的DPhPC的浅部分的酰基链，这被认为是一个重要的因素，在DPhPC膜的稳定性。
Diphytanoylphosphatidylcholine (DPhPC) is a synthetic phospholipid in which two methyl-branched acyl chains are introduced into the glycerol moiety, mimicking phospholipids of eukaryote and eubacteria origins. The lipid bilayers of DPhPC reproduce the outstanding physical properties of methyl-branched lipids that occur in archaea membranes. DPhPC is commonly used as the base lipid in biophysical experiments, particularly for recording ion-channel currents. However, the dynamics of lipid molecules that induces their useful physical properties is still unclear. In this study we examined the conformation and orientation of the methyl-branched acyl chain of DPhPC in membrane using 2H NMR measurements of the synthetic lipid with a high stereochemical purity and molecular dynamics (MD) simulations. Deuterium-labeled 3',3'-CD3,D-DPhPC (2) and 7',7'-CD3,D-DPhPC (3) showed the characteristic quadrupole splitting width in the 2H NMR spectra, which corresponded to the bent orientation reported for the archaeal lipid PGP-Me (Yamagami et al. Biochemistry 2019, 58, 3869-3879). However, MD simulations, which reproduced the 2H NMR results well, unveiled the unknown features of DPhPC in membrane; DPhPC has chain-specific average orientation, where two bent orientations with upward and downward methyl groups occur at the C3 and C7 positions of the sn-1 and sn-2 chains of DPhPC, respectively. These MD and NMR results reveal that these two bent orientations defines the average orientation of DPhPC for the shallow part of the acyl chains, which is considered to be an important factor in the stability of DPhPC membranes.