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Publication Abstract from PubMed

Transforming growth factor (TGF)-beta is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-beta1 requires the binding of alpha(v) integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-beta binding proteins. Crystals of dimeric porcine proTGF-beta1 reveal a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by receptors and alters its conformation. Complex formation between alpha(v)beta(6) integrin and the prodomain is insufficient for TGF-beta1 release. Force-dependent activation requires unfastening of a 'straitjacket' that encircles each growth-factor monomer at a position that can be locked by a disulphide bond. Sequences of all 33 TGF-beta family members indicate a similar prodomain fold. The structure provides insights into the regulation of a family of growth and differentiation factors of fundamental importance in morphogenesis and homeostasis.

Latent TGF-beta structure and activation.,Shi M, Zhu J, Wang R, Chen X, Mi L, Walz T, Springer TA Nature. 2011 Jun 15;474(7351):343-9. doi: 10.1038/nature10152. PMID:21677751^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.