S
Seetharaman Jayaraman
Publications - 1
Citations - 323
Seetharaman Jayaraman is an academic researcher. The author has contributed to research in topics: Protein domain & Heparan sulfate. The author has an hindex of 1, co-authored 1 publications receiving 229 citations.
Papers
More filters
Journal ArticleDOI
α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling
Gaozhi Chen,Yang Liu,Regina Goetz,Lili Fu,Lili Fu,Seetharaman Jayaraman,Ming Chang Hu,Orson W. Moe,Guang Liang,Xiaokun Li,Moosa Mohammadi +10 more
Abstract: The ageing suppressor α-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of α-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, α-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary complexes and receptor activation remain dependent on the binding of heparan sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of α-klotho is incompatible with its purported glycosidase activity. Thus, shed α-klotho functions as an on-demand non-enzymatic scaffold protein that promotes FGF23 signalling.