Chemokine receptor oligomerization and allostery.
Chemokine receptor oligomerization and allostery.
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DOI：
10.1016/b978-0-12-394587-7.00009-9
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发表时间：
2013
影响因子：
--
通讯作者：
Handel, Tracy M.
中科院分区：
文献类型：
--
作者：
Stephens, Bryan;Handel, Tracy M.
据报道，趋化因子受体的寡聚化通过受体原体之间的变构通讯影响受体功能的许多方面。趋化因子受体异寡聚物内的变构相互作用已被证明会导致趋化因子结合的负协同性，并在某些受体对的情况下抑制受体激活。其他受体对可以引起信号增强，甚至激活全新的异源寡聚物特异性信号复合物和受体激活下游的反应。许多机制促成这些效应，包括受体之间的直接变构偶联、G蛋白介导的变构、G蛋白窃取、配体隔离以及通过暴露寡聚受体上的独特结合界面来招募新的细胞内蛋白。这些效应对药物发现既带来了挑战，也带来了令人兴奋的机遇。最困难的挑战之一是确定异源寡聚物与同源寡聚物是否以及何时涉及特定的疾病状态。
Oligomerization of chemokine receptors has been reported to influence many aspects of receptor function through allosteric communication between receptor protomers. Allosteric interactions within chemokine receptor hetero-oligomers have been shown to cause negative cooperativity in the binding of chemokines and to inhibit receptor activation in the case of some receptor pairs. Other receptor pairs can cause enhanced signaling and even activate entirely new, hetero-oligomer-specific signaling complexes and responses downstream of receptor activation. Many mechanisms contribute to these effects including direct allosteric coupling between the receptors, G protein mediated allostery, G protein stealing, ligand sequestration and recruitment of new intracellular proteins by exposing unique binding interfaces on the oligomerized receptors. These effects present both challenges as well as exciting opportunities for drug discovery. One of the most difficult challenges will involve determining if and when hetero-oligomers versus homo-oligomers are involved in specific disease states.