# Latent-TGF-β has a domain swapped architecture

## TL;DR

This paper reveals the structural arrangement of the TGF-β latent complex, showing a domain-swapped architecture that explains how the protein becomes active.

## Contribution

The study provides definitive evidence for a domain-swapped architecture in the TGF-β latent complex.

## Key findings

- The prodomain of latent TGF-β has a domain-swapped architecture.
- This structural insight helps explain the activation mechanism of TGF-β.
- The domain-swapped configuration may influence how TGF-β is released or activated.

## 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.

TGF-β is a latent complex (L-TGF-β). Latency is conferred by a homodimeric prodomain with a previously undefined domain architecture. Here we define the architecture of the prodomain as domain-swapped providing structural insights into the mechanism of activation of L-TGF-β.