Laboratory for Biologically Inspired Computing, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka 565-0874, Japan.
School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Phys Rev E. 2020 Sep;102(3-1):032413. doi: 10.1103/PhysRevE.102.032413.
Eukaryotic cells transmit extracellular signal information to cellular interiors through the formation of a ternary complex made up of a ligand (or agonist), G-protein, and G-protein-coupled receptor (GPCR). Previously formalized theories of ternary complex formation have mainly assumed that observable states of receptors can only take the form of monomers. Here, we propose a multiary complex model of GPCR signaling activations via the vector representation of various unobserved aggregated receptor states. Our results from model simulations imply that receptor aggregation processes can govern cooperative effects in a regime inaccessible by previous theories. In particular, we show how the affinity of ligand-receptor binding can be largely varied by various oligomer formations in the low concentration range of G-protein stimulus.
真核细胞通过形成由配体（或激动剂）、G 蛋白和 G 蛋白偶联受体（GPCR）组成的三元复合物将细胞外信号信息传递到细胞内部。以前形成三元复合物的理论主要假设受体的可观察状态只能采取单体的形式。在这里，我们通过各种未观察到的聚合受体状态的向量表示，提出了 GPCR 信号激活的多元复合物模型。我们的模型模拟结果表明，受体聚集过程可以控制以前理论无法企及的协同作用。特别是，我们展示了在 G 蛋白刺激的低浓度范围内，通过各种寡聚体形成如何使配体-受体结合的亲和力在很大程度上发生变化。
