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重组FGF21的过度表达和生物物理和功能特征

Phuc Phan¹, Jason Hoang¹, Thallapuranam Krishnaswamy Suresh Kumar¹

¹Department of Chemistry and Biochemistry, Fulbright College of Art and Sciences, University of Arkansas, Fayetteville, Arkansas.

Biophysical reports

|January 30, 2025

概括

纤维细胞生长因子21 (FGF21) 对新陈代谢调节至关重要. 这项研究描述了重组FGF21 (rFGF21),揭示了它的结构,热不稳定性和代谢功能,为治疗代谢障碍提供了洞察力.

科学领域:

内分泌学在内分泌学.
蛋白质生物化学蛋白质生物化学
代谢研究研究代谢研究

背景情况:

纤维细胞生长因子21 (FGF21) 是一种关键的代谢调节剂,但其生物物理性质和稳定性尚未得到充分理解.
FGF21影响葡萄糖吸收,脂肪酸氧化和血糖水平,影响代谢疾病.

研究的目的:

描述可溶性重组FGF21 (rFGF21) 的生物物理特性,稳定性和代谢活性.
为工程 FGF21 变体提供基础,增强稳定性和对代谢障碍的治疗潜力.

主要方法:

可溶性重组FGF21 (rFGF21) 的过度表达和净化.
生物物理特征使用远紫外线循环二重化,差异扫描热量计和尿素诱导的展开.
酶消化试验 (素) 和结合研究 (异热定位热量计与肝素).
评估NIH/3T3纤维细胞和3T3-L1脂肪细胞中的代谢活性.

主要成果:

rFGF21表现出一种主要的β板形状和氨酸光.
rFGF21在温度上不稳定 (Tm = 46.8°C),易受尿素诱导的展开和素裂解.
rFGF21不会与肝素结合.
rFGF21促进纤维细胞的增殖,并增强 mitochondrial 氧化和脂肪酸氧化在脂肪细胞.

结论:

该研究提供了FGF21.21的第一个详细的生物物理和稳定性特征.
重组FGF21表现出显著的代谢活性,验证了其治疗潜力.
这些发现为开发更稳定,更强效的基于FGF21的代谢疾病治疗方法提供了框架.

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