Molecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity.

ABSTRACT:

Objective

To signal, FGF19 and FGF21 require co-receptor βKlotho (KLB) to act in concert with FGF receptors, and yet there is appreciable variance in the C-terminal sequences of these two novel metabolic hormones where binding is believed to be primary. We seek to determine the functional consequences for these amino acid differences and determine whether such information can be used to design high potency antagonists and agonists.

Methods

We employed a functional in vitro assay to identify C-terminal protein fragments capable of fully blocking KLB-mediated FGF19 and 21 receptor signaling. The key residues in each hormone responsible for support full bioactivity were identified through peptide-based Ala-scanning. Chemical optimization of the peptides was employed to increase

SUBMITTER: Agrawal A 

PROVIDER: S-EPMC6026317 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature