Latent-TGF-β has a domain swapped architecture

The multifunctional cytokine TGF-β is produced in a latent form (L-TGF-β) where a RGD containing homodimeric prodomain forms a “ring” encircling mature TGF-β shielding it from its receptors. Thus L-TGF-β must be activated to function, a process driven by dynamic allostery resulting from integrin binding the L-TGF-β RGD motif. Here we provide critical evidence that defines a domain-swapped architecture of L-TGF-β, an essential component in the dynamic allostery mechanism of L-TGF-β activation.