Year: 2025
Type: article
Abstract: The multifunctional cytokine TGF-β is a dimeric protein produced within a latent complex (L-TGF-β). Latency is maintained by disulfide linked homodimeric prodomains forming a ring encircling the non-covalently bound mature TGF-β homodimer. This configuration sterically inhibits mature TGF-β from binding to its receptors. For TGF-β to be activated and bind to its receptors it must either be released, or if not released, overcome steric hinderance within the latent complex. Integrin binding to L-TGF-β results in activation with or without release of TGF-β by deforming the ring through different yet incompletely understood mechanisms. The domain architecture of L-TGF-β, which is not clearly defined, is a gap in mechanistic understanding of L-TGF-β activation. Here we fill this critical gap-in-knowledge by definitive experimental evidence demonstrating a domain-swapped architecture of L-TGF-β.
Source: Nature Communications
Authors: Mingliang Jin, Robert I. Seed, Tiffany Shing, Li Wang, Junrui Li, Yifan Cheng, Stephen L. Nishimura
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Glacios™ Cryo Transmission Electron Microscope with 200 kV XFEG optics, G2369075306, Acquisition of an electron microscope for high-resolution single particle cryo-EM, G3820088598, G504053474, Structural mechanism of integrin-mediated TGF-b activation, Linux cluster for near atomic resolution single particle cryo-EM, GPU Computing Enabled Linux Computer Cluster, G9000003396, Conformational regulation of TGF-β activation by integrin αvβ6
OpenAlex ID: W4416631640