Directed Blocking of TGF-β Receptor I Binding Site Using Tailored Peptide Segments to Inhibit its Signaling Pathway.

ABSTRACT:

Background

TGF-β isoforms play crucial roles in diverse cellular processes. Therefore, targeting and inhibiting TGF-β signaling pathway provides a potential therapeutic opportunity. TGF-β isoforms bind and bring the receptors (TβRII and TβRI) together to form a signaling complex in an ordered manner.

Objectives

Herein, an antagonistic variant of TGF-β (AnTβ) has been designed and prepared to inhibit the formation of signaling complex and consequently its signaling pathway. This TGF-β homodimeric variant contains intact TβRII binding sites and blocked TβRI binding sites by substituting three peptide segments. So, AnTβ could only bind to TβRII, but prevent binding and recruitment of TβRI to form a signaling complex.

Materials and methods

A reliable model of AnTβ was bui

SUBMITTER: Sepehri S 

PROVIDER: S-EPMC7461711 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature