The role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices.
The role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices.
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膜介导的相互作用在化学感受器晶格的组装和结构中的作用。
DOI：
10.1371/journal.pcbi.1003932
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发表时间：
2014-12
影响因子：
4.3
通讯作者：
Wingreen NS
中科院分区：
文献类型：
--
作者：
Haselwandter CA;Wingreen NS
体内荧光显微镜和电子冷冻断层扫描表明，化学感受器自组装成化学感受器三聚体的延伸蜂窝状晶格，具有明确的三聚体相对方向。观察到的化学感受器晶格的信号响应因其极端的敏感性而引人注目，这在很大程度上依赖于化学感受器三聚体之间的协作相互作用。与其他膜蛋白一样，化学感受器三聚体预计会使周围的脂质双层变形，诱导相邻三聚体之间膜介导的各向异性相互作用。在这里，我们介绍了双层化学感受器相互作用的生物物理模型，该模型使我们能够量化膜介导的相互作用在化学感受器晶格的组装和结构中的作用。我们发现，即使没有直接的蛋白质-蛋白质相互作用，膜介导的相互作用也可以在非常稀的三聚体浓度下产生化学感受器晶格的组装。该模型正确预测了观察到的化学感受器晶格的蜂窝结构以及观察到的化学感受器三聚体的相对方向，提出了化学感受器晶格组装的一系列“网关”状态，并为大化学感受器晶格定位到细胞极提供了一种简单的机制。我们的双层化学感受器相互作用模型也有助于解释观察到的趋化信号对脂质双层特性的依赖性。最后，我们考虑膜介导的相互作用可能有助于相邻化学感受器三聚体之间的协同性。趋化系统使细菌能够对化学浓度的微小变化做出反应，并作为生物信号处理和活细胞中大型蛋白质晶格自组装的范例。趋化系统的敏感性主要依赖于化学感受器三聚体之间的协作相互作用，这些三聚体被组织成复杂的蜂窝状晶格。化学感受器是膜蛋白，因此预计会使周围的脂质双层变形，导致化学感受器三聚体之间膜介导的相互作用。使用双层化学感受器相互作用的生物物理模型，我们表明化学感受器三聚体诱导的膜介导的相互作用为观察到的化学感受器晶格的自组装提供了机制。我们发现，三聚体之间膜介导的相互作用的方向性补充了稳定观察到的化学感受器晶格蜂窝结构的蛋白质-蛋白质相互作用。我们的结果表明，化学感受器三聚体等膜蛋白复合物的对称性反映在膜介导的相互作用的各向异性中，从而产生了细胞膜中有序蛋白晶格自组装的一般机制。
In vivo fluorescence microscopy and electron cryo-tomography have revealed that chemoreceptors self-assemble into extended honeycomb lattices of chemoreceptor trimers with a well-defined relative orientation of trimers. The signaling response of the observed chemoreceptor lattices is remarkable for its extreme sensitivity, which relies crucially on cooperative interactions among chemoreceptor trimers. In common with other membrane proteins, chemoreceptor trimers are expected to deform the surrounding lipid bilayer, inducing membrane-mediated anisotropic interactions between neighboring trimers. Here we introduce a biophysical model of bilayer-chemoreceptor interactions, which allows us to quantify the role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices. We find that, even in the absence of direct protein-protein interactions, membrane-mediated interactions can yield assembly of chemoreceptor lattices at very dilute trimer concentrations. The model correctly predicts the observed honeycomb architecture of chemoreceptor lattices as well as the observed relative orientation of chemoreceptor trimers, suggests a series of “gateway” states for chemoreceptor lattice assembly, and provides a simple mechanism for the localization of large chemoreceptor lattices to the cell poles. Our model of bilayer-chemoreceptor interactions also helps to explain the observed dependence of chemotactic signaling on lipid bilayer properties. Finally, we consider the possibility that membrane-mediated interactions might contribute to cooperativity among neighboring chemoreceptor trimers. The chemotaxis system allows bacteria to respond to minute changes in chemical concentration, and serves as a paradigm for biological signal processing and the self-assembly of large protein lattices in living cells. The sensitivity of the chemotaxis system relies crucially on cooperative interactions among chemoreceptor trimers, which are organized into intricate honeycomb lattices. Chemoreceptors are membrane proteins and, hence, are expected to deform the surrounding lipid bilayer, leading to membrane-mediated interactions between chemoreceptor trimers. Using a biophysical model of bilayer-chemoreceptor interactions we show that the membrane-mediated interactions induced by chemoreceptor trimers provide a mechanism for the observed self-assembly of chemoreceptor lattices. We find that the directionality of membrane-mediated interactions between trimers complements protein-protein interactions in the stabilization of the observed honeycomb architecture of chemoreceptor lattices. Our results suggest that the symmetry of membrane protein complexes such as chemoreceptor trimers is reflected in the anisotropy of membrane-mediated interactions, yielding a general mechanism for the self-assembly of ordered protein lattices in cell membranes.
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影响因子：
2.9
作者：
Briegel A;Wong ML;Hodges HL;Oikonomou CM;Piasta KN;Harris MJ;Fowler DJ;Thompson LK;Falke JJ;Kiessling LL;Jensen GJ
通讯作者：
Jensen GJ
影响因子：
3.4
作者：
Brannigan, Grace;Brown, Frank L. H.
通讯作者：
Brown, Frank L. H.
影响因子：
3.6
作者：
Briegel, Ariane;Ding, H. Jane;Jensen, Grant J.
通讯作者：
Jensen, Grant J.
影响因子：
3.4
作者：
Endres, Robert G.
通讯作者：
Endres, Robert G.
影响因子：
3.4
作者：
Dan, N;Safran, SA
通讯作者：
Safran, SA