Schwyzer R, Moutevelis-Minakakis P, Kimura S, Gremlich H U
Institute of Molecular Biology and Biophysics, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland.
J Pept Sci. 1997 Jan-Feb;3(1):65-81. doi: 10.1002/(sici)1099-1387(199701)3:1<65::aid-psc90>3.0.co;2-q.
Lipid-induced secondary structures and orientations of the two enantiomeric [Leu5]-enkephalins, L-Tyr-Gly-Gly-L-Phe-L-Leu, and D-Tyr-Gly-Gly-D-Phe-D-Leu, on flat multi-bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were examined with polarized attenuated total reflection IR (IRATR) spectroscopy and molecular mechanics procedures. The membrane-bound peptides showed identical IR spectra in the amide I and II band regions that indicated membrane-induced secondary structures and specific orientations of the non-zwitterionic molecules. A Lorentzian band shape analysis based on second derivatives of the original curves and observed band polarizations suggested the presence of helical structures (beta III- and alpha-turns), oriented more or less perpendicular to the membrane surface. Other folded structures, e.g. beta I- and gamma turns, were not excluded. Molecular modelling of non-zwitterionic (Leu5)-enkephalin with two beta III-turns or an alpha-turn resulted in essentially four low-energy conformers containing (i) two beta III-turns, (ii) one alpha-turn, (iii) a beta III-turn fused to an alpha-turn, and (iv) a beta III-turn fused to a beta I-turn as in the crystallographic molecular conformation described by Aubry et al. [Biopolymers 28, 27-40 (1989)]. Zwitterionic [Leu5]-enkephalin with two beta III-turns collapsed to a C13 turn (a distorted alpha-turn) bridged by a gamma I-turn (v). The alignment of the amide I oscillators within the helical structures, (i), (ii) and (iii), and the double-bend structures, (iv) and (v), explained the observed amide I and II polarizations. Differences between these and other lipid-induced [Leu5]-enkephalin conformers reported in the literature may be caused by the lipid polymorphism of the model membranes used. Possible implications of the new conformers for the molecular mechanism of opioid receptor selection are discussed in terms of the membrane compartments theory.
利用偏振衰减全反射红外光谱（IRATR）和分子力学方法，研究了两种对映体[亮氨酸5]脑啡肽（L-酪氨酸-甘氨酸-甘氨酸-L-苯丙氨酸-L-亮氨酸和D-酪氨酸-甘氨酸-甘氨酸-D-苯丙氨酸-D-亮氨酸）在1-棕榈酰-2-油酰基-sn-甘油-3-磷酸胆碱（POPC）平面多层膜上由脂质诱导产生的二级结构和取向。膜结合肽在酰胺I和II带区域显示出相同的红外光谱，这表明非两性离子分子的膜诱导二级结构和特定取向。基于原始曲线的二阶导数和观察到的谱带偏振进行的洛伦兹带形状分析表明存在螺旋结构（βIII-和α-转角），其或多或少垂直于膜表面取向。其他折叠结构，如βI-和γ-转角，并未被排除。具有两个βIII-转角或一个α-转角的非两性离子[亮氨酸5]脑啡肽的分子建模产生了基本上四个低能量构象，包括（i）两个βIII-转角；（ii）一个α-转角；（iii）一个与α-转角融合的βIII-转角；以及（iv）一个与βI-转角融合的βIII-转角，如同奥布里等人所描述的晶体学分子构象[《生物聚合物》28, 27 - 40 (1989)]。具有两个βIII-转角的两性离子[亮氨酸5]脑啡肽折叠成一个由γI-转角桥接的C13转角（一种扭曲的α-转角）（v）。螺旋结构（i）、（ii）和（iii）以及双弯结构（iv）和（v）内酰胺I振荡器的排列解释了观察到的酰胺I和II偏振。这些构象与文献中报道的其他脂质诱导的[亮氨酸5]脑啡肽构象之间的差异可能是由所用模型膜的脂质多态性引起的。根据膜区室理论讨论了新构象对阿片受体选择分子机制的可能影响。
