| | FGF21 N- and C-termini play different roles in receptor interaction and activationEdited by Gianni Cesareni Received 11 September 2008; received in revised form 20 October 2008; accepted 9 November 2008. published online 05 December 2008. Abstract Fibroblast growth factor-21 (FGF21) signaling requires the presence of β-Klotho, a co-receptor with a very short cytoplasmic domain. Here we show that FGF21 binds directly to β-Klotho through its C-terminus. Serial C-terminal truncations of FGF21 weakened or even abrogated its interaction with β-Klotho in a Biacore assay, and led to gradual loss of potency in a luciferase reporter assay but with little effect on maximal response. In contrast, serial N-terminal truncations of FGF21 had no impact on β-Klotho binding. Interestingly, several of them exhibited characteristics of partial agonists with minimal effects on potency. These data demonstrate that the C-terminus of FGF21 is critical for binding to β-Klotho and the N-terminus is critical for fibroblast growth factor receptor (FGFR) activation. a Department of Metabolic Disorders, Amgen Inc., One Amgen Center Drive, Mail Stop 29-1-A, Thousand Oaks, CA 91320, USA b Department of Protein Science, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA  Corresponding author. Fax: +1 805 499 0953.
PII: S0014-5793(08)00935-6 doi:10.1016/j.febslet.2008.11.023 © 2008 Federation of European Biochemical Societies | |
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ABSTRACT
