Bindings of hMRP1 transmembrane peptides with dodecylphosphocholine and dodecyl-β-D-maltoside micelles: A molecular dynamics simulation study
Bindings of hMRP1 transmembrane peptides with dodecylphosphocholine and dodecyl-β-D-maltoside micelles: A molecular dynamics simulation study
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DOI：
10.1016/j.bbamem.2013.10.012
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发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Marchi, Massimo
中科院分区：
文献类型：
--
作者：
Abel, Stephane;Lorieau, Anais;Marchi, Massimo
在本文中，我们描述了四种肽（mTM10、mTM16、TM17和KTM17）与十二烷基磷酸胆碱（DPC）和十二烷基-β-D-麦芽糖苷（DDM）胶束之间相互作用的分子动力学模拟结果。这些肽代表来自 ABC 膜蛋白 (hMRP1) 的 MSD1 和 MSD2 跨膜结构域的三个跨膜片段（TM10、16 和 17），它们在蛋白质功能中发挥作用。将肽-胶束复合物结构（包括色氨酸可及性和动力学）与在水、三氟乙醇和胶束中获得的圆二色性和荧光研究进行比较。我们的工作提供了实验无法直接获得的额外结果，进一步支持了这些肽在胶束内采用界面构象的事实。我们还表明，肽在 DDM 中比在 DPC 中埋藏得更多，因此，它们在 DPC 中比在 DDM 中暴露于水的表面更大。正如之前通过模拟和实验所指出的，我们还观察到磷酸胆碱 DPC 头基和色氨酸肽残基之间形成了阳离子-π 键。关于肽二级结构（SS），我们发现在 TFE 中，它们的初始螺旋构象在模拟过程中保持不变，而在水中，它们的初始 SS 在模拟几纳秒后就丢失了。在胶束中观察到一种中间情况，其中肽在 DDM 中保持部分折叠，并且比在 DPC 中更加结构化。最后，我们的结果表明，即使在水中或胶束中模拟三个相同的肽，也没有远紫外 CD 实验引发的 β 链结构形成的迹象。 (C) 2013 Elsevier B.V. 保留所有权利。
In this paper, we describe molecular dynamics simulation results of the interactions between four peptides (mTM10, mTM16, TM17 and KTM17) with micelles of dodecylphosphocholine (DPC) and dodecyl-beta-D-maltoside (DDM). These peptides represent three transmembrane fragments (TM10, 16 and 17) from the MSD1 and MSD2 membrane-spanning domains of an ABC membrane protein (hMRP1), which play roles in the protein functions. The peptide-micelle complex structures, including the tryptophan accessibility and dynamics were compared to circular dichroism and fluorescence studies obtained in water, trifluoroethanol and with micelles. Our work provides additional results not directly accessible by experiments that give further support to the fact that these peptides adopt an interfacial conformation within the micelles. We also show that the peptides are more buried in DDM than in DPC, and consequently, that they have a larger surface exposure to water in DPC than in DDM. As noted previously by simulations and experiments we have also observed formation of cation-pi bonds between the phosphocholine DPC headgroup and Trp peptide residue. Concerning the peptide secondary structures (SS), we find that in TFE their initial helical conformations are maintained during the simulation, whereas in water their initial SS are lost after few nanoseconds of simulation. An intermediate situation is observed with micelles, where the peptides remain partially folded and more structured in DDM than in DPC. Finally, our results show no sign of beta-strand structure formation as invoked by far-UV CD experiments even when three identical peptides are simulated either in water or with micelles. (C) 2013 Elsevier B.V. All rights reserved.