Ossa Felipe, Schnell Jason R, Ortega-Roldan José Luis
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
School of Biosciences, University of Kent, Stacey Building, Room 215B, Canterbury, CT2 7NJ, UK.
Adv Exp Med Biol. 2017;964:15-29. doi: 10.1007/978-3-319-50174-1_3.
The Sigma-1 Receptor (S1R) is a small, ligand-regulated integral membrane protein involved in cell homeostasis and the cellular stress response. The receptor has a multitude of protein and small molecule interaction partners with therapeutic potential. Newly reported structures of the human S1R in ligand-bound states provides essential insights into small molecule binding in the context of the overall protein structure. The structure also raises many interesting questions and provides an excellent starting point for understanding the molecular tricks employed by this small membrane receptor to modulate a large number of signaling events. Here, we review insights from the structures of ligand-bound S1R in the context of previous biochemical studies and propose, from a structural viewpoint, a set of important future directions.
西格玛-1受体（S1R）是一种小型的、受配体调节的整合膜蛋白，参与细胞内稳态和细胞应激反应。该受体有众多具有治疗潜力的蛋白质和小分子相互作用伙伴。新报道的人S1R在配体结合状态下的结构为在整体蛋白质结构背景下理解小分子结合提供了重要见解。该结构还提出了许多有趣的问题，并为理解这个小膜受体用于调节大量信号事件的分子机制提供了一个绝佳的起点。在此，我们结合先前的生化研究，综述来自配体结合S1R结构的见解，并从结构角度提出一系列重要的未来研究方向。
