Latent-TGF-β has a domain swapped architecture
Open accessPublished version of a preprint
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.
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Cites
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- Authors
- Jin, M., Seed, R. I., Shing, T., Wang, L., Li, J., Cheng, Y., & Nishimura, S. L.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Cheng, Yifan
- Nishimura, Stephen L.
- Venue
- Nature Communications
- Published
- 2025-11-25
- Volume
- 16
- Issue
- 1
- Pages
- 10469-10469
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11581116
- OpenAlex
- W4416631640
- Cited by
- 3
- References
- 4
- Citations by year
- 2026: 3
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (R01 HL165175, R01 HL134183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- latent TGF-beta, TGF-beta activation, domain swapping, integrin binding, steric inhibition, protein dimerization, disulfide-linked homodimer
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