Bacterial Analogs to Cholesterol Affect Dimerization of Proteorhodopsin and Modulates Preferred Dimer Interface
Bacterial Analogs to Cholesterol Affect Dimerization of Proteorhodopsin and Modulates Preferred Dimer Interface
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胆固醇的细菌类似物影响蛋白视紫红质的二聚化并调节优选的二聚体界面
DOI：
10.1021/acs.jctc.0c01174
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发表时间：
2021
影响因子：
5.5
通讯作者：
Mertz, Blake
中科院分区：
文献类型：
--
作者：
Sefah, Eric;Mertz, Blake
霍烷类化合物是甾醇的细菌类似物，在细菌中普遍存在，在应激环境下的生物体生存中发挥着重要作用。与甾醇不同，藿类化合物的环部分取代基的大小和化学性质存在很大差异，从而对生物膜的结构和动力学产生不同的影响。虽然人们知道藿香类化合物可以间接调节膜的物理性质，但人们对藿香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，我们使用粗粒度分子动力学模拟来表征两种藿烷类化合物，二聚丁烯（DPT）和细菌藿烷四醇（BHT）对由1-棕榈酰-2-油酰-sn-甘油-3-磷酸乙醇胺（POPE）和1-棕榈酰-2-油酰-sn-3-磷酸甘油（POPG）。 PR 是一种细菌膜蛋白，具有光激活质子泵的作用。我们选择 PR 是因为它能够在不同的膜环境中采用寡聚状态的分布。此外，PR 中质子泵送的效率与其组织成低聚物密切相关。我们的结果表明，BHT 和 DPT 通过以浓度依赖性方式调节膜特性来间接影响二聚化。它们与膜嵌入区域和细胞质区域中的 PR 相互作用的变化导致对二聚体界面的可塑性产生明显不同的影响。 BHT 能够在二聚体界面的单体之间插入，而 DPT 通过堆积膜的小叶区域来改变二聚化相互作用。我们的结果显示了霍帕尼结构与 PR 的横向组织之间的直接关系，使人们首次了解这些真核甾醇的细菌类似物如何在细胞膜内产生非常相似的生物物理效应。
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-sn-glycero-3-phophoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-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.