Dynamic allostery: a novel mechanism regulating autocrine and paracrine TGF-β signalling
2024

Dynamic Allostery in TGF-β Signaling

publication Evidence: high

Author Information

Author(s): Hendrik Ungefroren, Jens Uwe Marquardt

Primary Institution: University Hospital Schleswig-Holstein (UKSH), Campus Lübeck

Hypothesis

Can TGF-β1 induce signaling in a non-activated form while still residing in a complex?

Conclusion

The study reveals that TGF-β1 can signal without being released from its latent form, challenging previous understandings of its activation.

Supporting Evidence

  • TGF-β1 can signal without being released from its latent form.
  • Dynamic allostery explains the mechanism of TGF-β3 latency and activation.
  • Targeting TGF-β activation through CER offers opportunities for directional context-dependent TGF-β activation.

Takeaway

This study shows that TGF-β1 can work even when it's not fully activated, which could change how we think about treating diseases like cancer.

Methodology

The authors used advanced methods and genetic mouse models to study TGF-β signaling.

Limitations

The study does not clarify how LTBP affects intrinsic flexibility or CER, which requires further investigation.

Digital Object Identifier (DOI)

10.1038/s41392-024-02099-2

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