Institute of Pharmacy, Martin-Luther-University, Halle, Germany.
Br J Pharmacol. 2020 Apr;177(7):1485-1496. doi: 10.1111/bph.14991. Epub 2020 Feb 11.
ABCG2 belongs to the ABC transporter superfamily and functions as a poly-specific efflux pump. As it can transport a broad spectrum of substrates out of cells, ABCG2 is thought to alter the pharmacokinetics of drugs applied to treat certain diseases. Especially, its potential to induce resistance to chemotherapy is currently the object of intense research. To foster understanding of mechanisms relevant for substrate recognition and selection of ABCG2 substrates and to finally develop selective therapeutic modulators (e.g. inhibitors) of ABCG2 transport activity, it is important to further explore the precise 3D structure of the transporter. While efforts to elucidate the three-dimensional structure of ABCG2 using X-ray crystal structure analysis have not been successful so far, high-resolution cryo-electron microscopy-based investigations have revealed exciting new insights into the structure and function of the transporter. In this review, we will focus on these seminal publications to summarize the current understanding of tertiary and quaternary structure, homodimerization or oligomerization, and functions of the ABCG2 transporter protein.
ABCG2 属于 ABC 转运体超家族，作为一种多特异性外排泵发挥作用。由于它可以将广泛的底物从细胞内转运出去，因此 ABCG2 被认为可以改变用于治疗某些疾病的药物的药代动力学。特别是，它诱导化疗耐药的潜力目前是研究的重点。为了促进对底物识别和 ABCG2 底物选择相关机制的理解，并最终开发 ABCG2 转运活性的选择性治疗调节剂（例如抑制剂），进一步探索转运体的确切 3D 结构非常重要。虽然使用 X 射线晶体结构分析阐明 ABCG2 的三维结构的努力迄今尚未成功，但基于高分辨率冷冻电子显微镜的研究揭示了转运体结构和功能的令人兴奋的新见解。在这篇综述中，我们将重点介绍这些开创性的出版物，以总结 ABCG2 转运蛋白的三级和四级结构、同源二聚体或寡聚化以及功能的当前认识。
