成纤维细胞生长因子受体（FGFRs）属于细胞表面受体型酪氨酸激酶(receptor tyrosine kinase，RTK)，在细胞增殖与分化等一系列正常生命活动过程中发挥关键调控作用。FGF21作为一种非典型性成纤维细胞生长因子,可以调节人体内一些重要的代谢过程特别是糖的代谢,是治疗二型糖尿病的潜在药物,然而其结构与调控糖脂代谢的机制亟待阐明。本项目拟依托中国科学院强磁场科学中心的高场核磁共振研究平台, 在获得FGF21以及FGFR1c三维结构的基础上，在近生理膜环境下综合应用多种生物物理技术研究FGFR1c受体与FGF21等配体的特异性识别，阐明不同配体诱导的FGFR1c构象变化与其胞内区自磷酸化模式之间的相关性。FGFR1c介导的跨膜信号转导机制的研究将有助于了解相关疾病的发病机理，为新型二型糖尿病的药物开发奠定理论基础。

Fibroblast growth factor receptors (FGFRs) are trans-membrane tyrosine kinase receptors activated by a unique subset of Fibroblast growth factors (FGFs). The large number of FGF and FGFR variants and their widespread expression provide the FGF/FGFR signaling system with functional diversity and reflect their many important roles during development as well as in the adult organism. Fibroblast growth factor 21 (FGF21) is a newly discovered atypical member of the FGF family that functions as an endocrine hormone. Pharmacologic studies have demonstrated that FGF21 might be an important type II diabetes drug candidate. In this proposal we will take the advantage of the advanced high magnetic field instruments especially high resolution liquid state NMR, to elucidate the structural bases for the specific binding of FGF21 to FGFR1c, and the cross-membrane signal transduction mechanism of FGFR1c in a native membrane mimic enviroment. The novelty of this study is highlighted in the integration of multiple technologies and multiple scientific fields. We anticipate this study would pave the road for developing novel mechanism and effective anti-type II diabetic therapies.