Nanobody stabilization of G protein-coupled receptor conformational states.
Nanobody stabilization of G protein-coupled receptor conformational states.
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DOI：
10.1016/j.sbi.2011.06.011
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发表时间：
2011-08
影响因子：
6.8
通讯作者：
Kobilka BK
中科院分区：
文献类型：
--
作者：
Steyaert J;Kobilka BK
G蛋白偶联受体（GPCR）结构生物学研究在过去的四年中取得了显著的进展。通过结合从蛋白质工程到基于脂质的筛选和微衍射技术的创新方法，已经克服了产生GPCR的衍射质量晶体的几个障碍。初始GPCR结构代表能量稳定的非活性态构象。然而，GPCR信号通过不同的G蛋白异构体或G蛋白独立的效应物后，配体结合表明存在多个配体特异性的活性状态。这些活性状态的构象是不稳定的，在特定的胞质信号的合作伙伴代表结构生物学的新挑战。骆驼科动物单链抗体片段（纳米抗体）显示出稳定活性GPCR构象和作为晶体发生的伴侣的前景。
Remarkable progress has been made in the field of G protein coupled receptor (GPCR) structural biology during the past four years. Several obstacles to generating diffraction quality crystals of GPCRs have been overcome by combining innovative methods ranging from protein engineering to lipid-based screens and microdiffraction technology. The initial GPCR structures represent energetically stable inactive-state conformations. However, GPCRs signal through different G protein isoforms or G protein-independent effectors upon ligand binding suggesting the existence of multiple ligand-specific active states. These active-state conformations are unstable in the absence of specific cytosolic signaling partners representing new challenges for structural biology. Camelid single chain antibody fragments (nanobodies) show promise for stabilizing active GPCR conformations and as chaperones for crystallogenesis.