Department of Molecular and Cellular Interactions, Vlaams Instituut voor Biotechnologie & Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.
Curr Opin Struct Biol. 2011 Aug;21(4):567-72. doi: 10.1016/j.sbi.2011.06.011. Epub 2011 Jul 21.
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.
在过去的四年中，G 蛋白偶联受体（GPCR）结构生物学领域取得了显著进展。通过结合从蛋白质工程到基于脂质的筛选和微衍射技术等创新方法，克服了生成 GPCR 衍射质量晶体的几个障碍。最初的 GPCR 结构代表了能量稳定的无活性状态构象。然而，GPCR 通过配体结合后通过不同的 G 蛋白同工型或 G 蛋白独立效应器信号转导，这表明存在多种配体特异性的活性状态。这些活性状态构象在没有特定的细胞溶质信号伴侣的情况下是不稳定的，这代表了结构生物学的新挑战。骆驼科单链抗体片段（纳米抗体）有望稳定活性 GPCR 构象，并作为结晶的伴侣。
