Abel Stéphane, Lorieau Anaïs, de Foresta Béatrice, Dupradeau François-Yves, Marchi Massimo
Commissariat à l'Energie Atomique et aux Energies Alternatives, DSV/iBiTEC-S/SB2SM/LBMS & CNRS UMR 8221, Saclay, France.
Biochim Biophys Acta. 2014 Jan;1838(1 Pt B):493-509. doi: 10.1016/j.bbamem.2013.10.012. Epub 2013 Oct 21.
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-β-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-π 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 β-strand structure formation as invoked by far-UV CD experiments even when three identical peptides are simulated either in water or with micelles.
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ABC膜蛋白（hMRP1）的MSD1和MSD2跨膜结构域中的三个跨膜片段（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了比较。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中采取界面构象这一事实。我们还表明，肽在DDM中比在DPC中埋藏得更深，因此，它们在DPC中比在DDM中与水的表面接触更大。如先前通过模拟和实验所指出的，我们还观察到磷酸胆碱DPC头部基团与色氨酸肽残基之间形成了阳离子-π键。关于肽的二级结构（SS），我们发现，在三氟乙醇中，它们的初始螺旋构象在模拟过程中得以维持，而在水中，模拟几纳秒后它们的初始二级结构就会丧失。在胶束中观察到一种中间情况，其中肽在DDM中比在DPC中保持部分折叠且结构更有序。最后，我们的结果表明，即使在水中或与胶束一起模拟三个相同的肽，也没有远紫外圆二色性实验所推测的β-链结构形成的迹象。
