Agonistic β-Klotho antibody mimics fibroblast growth factor 21 (FGF21) functions.

ABSTRACT: Fibroblast growth factor 21 (FGF21), an endocrine hormone in the FGF family, plays a critical role in regulating metabolic homeostasis and has emerged as a therapeutic target for metabolic diseases, including Type 2 diabetes mellitus. FGF21 functions through a receptor complex that consists of an FGF receptor (FGFR) and a co-receptor β-Klotho. Here, we identify and biochemically and structurally characterize 39F7, a high-affinity agonistic monoclonal antibody (mAb) against β-Klotho that mimics FGF21 function. The co-crystal structure of β-Klotho KL1 domain in complex with 39F7 Fab revealed that the recognition of 39F7 is centered on Trp-295 of β-Klotho in a FGF21 noncompetitive manner. KL1 adopts a (β/α)₈ TIM barrel fold which resembles that of β-glycosylceramidase, but lacks mo

SUBMITTER: Min X 

PROVIDER: S-EPMC6153294 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature