The follicle-stimulating hormone receptor (FSHR) belongs to the glycoprotein hormone receptors, a subfamily of G-protein-coupled receptors (GPCRs). FSHR is involved in reproductive processes such as gonadal development and maturation. Structurally, the extensive extracellular domain, which contains the hormone-binding site and is linked to the transmembrane domain by the hinge region (HR), is characteristic for these receptors. How this HR is involved in hormone binding and signal transduction is still an open question. We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data with molecular modeling to generate experimentally driven full-length models. These models provide insights into the interface, important side-chain interactions, and activation mechanism. The interface indicates a strong involvement of the connecting loop. A major rearrangement of the HR seems implausible due to the tight arrangement and fixation by disulfide bonds. The models are expected to allow for testable hypotheses about signal transduction and drug development for GPHRs.

促卵泡激素受体 (FSHR) 属于糖蛋白激素受体，是 G 蛋白偶联受体 (GPCR) 的一个亚家族。FSHR 参与生殖过程，例如性腺发育和成熟。在结构上，包含激素结合位点并通过铰链区 (HR) 连接到跨膜结构域的广泛细胞外结构域是这些受体的特征。这种 HR 如何参与激素结合和信号转导仍然是一个悬而未决的问题。我们结合了体外和原位化学交联、二硫键模式分析和分子建模的突变数据，以生成实验驱动的全长模型。这些模型提供了对界面、重要的侧链交互和激活机制的洞察。该界面表明连接回路的强烈参与。由于二硫键的紧密排列和固定，HR 的主要重排似乎不可信。预计这些模型将允许关于 GPHR 的信号转导和药物开发的可检验假设。