C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506, United States.
WVU Cancer Institute, West Virginia University, Morgantown, West Virginia 26506, United States.
J Chem Theory Comput. 2021 Apr 13;17(4):2502-2512. doi: 10.1021/acs.jctc.0c01174. Epub 2021 Mar 31.
Hopanoids, the bacterial analogues of sterols, are ubiquitous in bacteria and play a significant role in organismal survival under stressful environments. Unlike sterols, hopanoids have a high degree of variation in the size and chemical nature of the substituent attached to the ring moiety, leading to different effects on the structure and dynamics of biological membranes. While it is understood that hopanoids can indirectly tune membrane physical properties, little is known on the role that hopanoids may play in affecting the organization and behavior of bacterial membrane proteins. In this work we used coarse-grained molecular dynamics simulations to characterize the effects of two hopanoids, diploptene (DPT) and bacteriohopanetetrol (BHT), on the oligomerization of proteorhodopsin (PR) in a model membrane composed of 1-palmitoyl-2-oleoyl--glycero-3-phophoethanolamine (POPE) and 1-palmitoyl-2-oleoyl--3-phosphoglycerol (POPG). PR is a bacterial membrane protein that functions as a light-activated proton pump. We chose PR based on its ability to adopt a distribution of oligomeric states in different membrane environments. Furthermore, the efficiency of proton pumping in PR is intimately linked to its organization into oligomers. Our results reveal that both BHT and DPT indirectly affect dimerization by tuning membrane properties in a fashion that is concentration-dependent. Variation in their interaction with PR in the membrane-embedded and the cytoplasmic regions leads to distinctly different effects on the plasticity of the dimer interface. BHT has the ability to intercalate between monomers in the dimeric interface, whereas DPT shifts dimerization interactions via packing of the interleaflet region of the membrane. Our results show a direct relationship between hopanoid structure and lateral organization of PR, providing a first glimpse at how these bacterial analogues to eukaryotic sterols produce very similar biophysical effects within the cell membrane.
藿烷类化合物是甾醇的细菌类似物，广泛存在于细菌中，在应激环境下对生物的生存起着重要作用。与甾醇不同的是，藿烷类化合物在环部分连接的取代基的大小和化学性质上具有高度的可变性，导致对生物膜结构和动力学的不同影响。虽然人们知道藿烷类化合物可以间接调节膜的物理性质，但对于藿烷类化合物在影响细菌膜蛋白的组织和行为方面可能发挥的作用知之甚少。在这项工作中，我们使用粗粒化分子动力学模拟来表征两种藿烷类化合物，二萜（DPT）和细菌藿烷四醇（BHT），对模型膜中蛋白视紫红质（PR）寡聚化的影响，该模型膜由 1-棕榈酰-2-油酰基-甘油-3-磷酸乙醇胺（POPE）和 1-棕榈酰-2-油酰基-3-磷酸甘油（POPG）组成。PR 是一种细菌膜蛋白，作为光激活质子泵发挥作用。我们选择 PR 是基于它在不同膜环境中能够采用多种寡聚状态分布的能力。此外，PR 中质子泵的效率与其寡聚化密切相关。我们的结果表明，BHT 和 DPT 都通过以浓度依赖的方式调节膜性质间接影响二聚体的形成。它们在膜嵌入和细胞质区域与 PR 的相互作用的变化导致对二聚体界面可塑性的截然不同的影响。BHT 能够在二聚体界面的单体之间插入，而 DPT 通过膜的层间区域的堆积来改变二聚化相互作用。我们的结果显示了藿烷类化合物结构与 PR 侧向组织之间的直接关系，为这些细菌类似物与真核甾醇在细胞膜内产生非常相似的生物物理效应提供了初步的了解。
