GEMPPO, Departamento de Física Macromolecular, Instituto de Estructura de la Materia, CSIC, Serrano 113bis, 28006, Madrid, Spain.
Phys Chem Chem Phys. 2011 Mar 7;13(9):3660-8. doi: 10.1039/c0cp01456g. Epub 2010 Dec 21.
Cannabinoid receptors CB1 and CB2 are a striking class of transmembrane proteins involved in a high number of important biological processes. In spite of the inherent similarity (40% in aminoacid sequence) these receptors are found in different cell environments. In addition to this, CB1 activity has been intimately associated with lipid rafts whereas CB2 has not. In this work we have performed a 50 nanosecond molecular dynamics simulation of the inactive conformations of both receptors inserted in a POPC lipid bilayer. Although in both cases the overall protein structure is maintained along the entire simulation we have found important differences in the protein-lipid interaction. While CB1 tends to distort the lipid bilayer regularity, especially in the extracellular moiety, CB2 has a minor influence on the lipid distribution along the plane of the bilayer. This observation is consistent with some experimental facts observed in these cannabinoid receptors with regard to lipid/protein interaction.
大麻素受体 CB1 和 CB2 是一类在许多重要生物过程中发挥作用的跨膜蛋白，它们具有显著的特点。尽管这些受体在氨基酸序列上具有 40%的相似性，但它们存在于不同的细胞环境中。此外，CB1 的活性与脂筏密切相关，而 CB2 则没有。在这项工作中，我们对插入 POPC 脂质双层中的两种受体的非活性构象进行了 50 纳秒的分子动力学模拟。尽管在这两种情况下，整个蛋白质结构在整个模拟过程中都得到了维持，但我们发现了蛋白质-脂质相互作用的重要差异。虽然 CB1 倾向于扭曲脂质双层的规则性，特别是在细胞外部分，但是 CB2 对脂质在双层平面上的分布的影响较小。这一观察结果与这些大麻素受体在脂质/蛋白质相互作用方面的一些实验事实是一致的。
