Structural Analysis of the Smad2−MAN1 Interaction That Regulates Transforming Growth Factor-β Signaling at the Inner Nuclear Membrane

摘要: MAN1, an integral protein of the inner nuclear membrane, influences transforming growth factor-β (TGF-β) signaling by directly interacting with R-Smads. Heterozygous loss function mutations in gene encoding MAN1 cause sclerosing bone dysplasias and increased level TGF-β cells. As a first step elucidating mechanism pathway regulation we characterized structure C-terminal region that binds Smad2. Using magnetic resonance spectroscopy, observed this is comprised winged helix domain, structurally heterogeneous linker, U2AF homology motif (UHM) disordered C-terminus. From small-angle X-ray scattering data, calculated family models for region. Our data indicate linker plays role intramolecular UHM ligand (ULM) domain. We mapped Smad2 binding site onto combining GST pull-down, f...