Since the discovery of mutations in leucine-rich repeat kinase 2 (LRRK2) as an underlying genetic cause for the development of Parkinson's disease (PD) in 2004 (Neuron 44, 601–607; Neuron 44, 595–600), and subsequent efforts to develop LRRK2 kinase inhibitors as a therapy for Parkinson's (Expert Opin. Ther. Targets 21, 751–753), elucidating the atomic resolution structure of LRRK2 has been a major goal of research into this protein. At over 250 kDa, the large size and complicated domain organisation of LRRK2 has made this a highly challenging target for structural biologists, however, a number of recent studies using both in vitro and in situ approaches (Nature 588, 344–349; Cell 182, 1508–1518.e1516; Cell 184, 3519–3527.e3510) have provided important new insights into LRRK2 structure and the complexes formed by this protein.

中文翻译：

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从结构到病因学：富含亮氨酸重复激酶 2 和帕金森病生物学的新窗口

自 2004 年发现富含亮氨酸重复激酶 2 (LRRK2) 的突变作为帕金森病 (PD) 发展的潜在遗传原因以来（神经元 44, 601–607；神经元 44, 595–600），以及随后的努力开发 LRRK2 激酶抑制剂作为帕金森病的治疗方法（Expert Opin. Ther. Targets 21, 751–753），阐明 LRRK2 的原子分辨率结构一直是研究该蛋白质的主要目标。在超过 250 kDa 时，LRRK2 的大尺寸和复杂的结构域组织使其成为结构生物学家极具挑战性的目标，然而，最近的一些研究使用体外和原位方法（Nature 588、344–349；Cell 182 , 1508–1518.e1516; Cell 184, 3519–3527.e3510) 为 LRRK2 结构和由该蛋白形成的复合物提供了重要的新见解。