Research progress on the structural basis and biased signaling of fibroblast growth factor-receptor protein interactions
10.11665/j.issn.1000-5048.2026073001
- VernacularTitle:成纤维细胞生长因子及其受体蛋白相互作用的结构基础与信号偏向性研究进展
- Author:
Jie QI
1
;
Yufeng LI
;
Shuliang TIAN
;
Lintao SONG
;
Zhifeng HUANG
Author Information
1. 温州医科大学药学院, 温州325035
- Publication Type:Journal Article
- Keywords:
FGF-FGFR;
protein-protein interactions;
biased signaling;
precision drug design
- From:
Journal of China Pharmaceutical University
2026;57(5):575-584
- CountryChina
- Language:Chinese
-
Abstract:
Fibroblast growth factors (FGFs) and their receptors, fibroblast growth factor receptors (FGFRs), constitute an essential signaling system that is widely involved in development, tissue homeostasis, and metabolic regulation. In recent years, advances in cryo-electron microscopy and protein engineering have shifted FGF-FGFR research from the traditional receptor activation paradigm toward a new framework centered on protein-protein interactions and receptor conformation-mediated signaling bias. This review summarizes the structural basis of FGF-FGFR protein interactions, with particular emphasis on the asymmetric dimer model, the distinct receptor recognition mechanisms of paracrine and endocrine FGFs, and recent progress in the receptor dimerization threshold model. It further discusses the molecular mechanisms underlying FGFR signaling bias and summarizes recent progress in the design of engineered FGF analogs and FGFR agonists, aiming to provide new theoretical insights for precision therapies for metabolic diseases.
