Understanding the Physical Interactions in the FGF21/FGFR/β-Klotho Complex: Structural Requirements and Implications in FGF21 Signaling (pages 398–410)
Junming Yie, Wei Wang, Liying Deng, Lei-Ting Tam, Jennitte Stevens, Michelle M. Chen, Yang Li, Jing Xu, Richard Lindberg, Randy Hecht, Murielle Véniant, Ching Chen and Minghan Wang
Article first published online: 1 FEB 2012 | DOI: 10.1111/j.1747-0285.2012.01325.x
(i) Deletion of the D1/linker region (the D1 and the D1-D2 linker) from FGFR1c led to β-Klotho-independent receptor activation by FGF21, and the D1/linker region of FGFR1c inhibited β-Klotho/FGFR1c interaction. (ii) Deletion of the D1/linker region enhanced the formation of the FGF21/β-Klotho/FGFR1c ternary complex in both Biacore and asymmetrical flow field flow fractionation studies. (iii) The N-terminus of FGF21 directly mediated FGFR1c activation, and the N-terminus of FGF21 is involved in the interaction with FGFR1c and FGF21/β-Klotho/FGFR1c ternary complex formation.