期刊
NATURE
卷 474, 期 7351, 页码 343-U370出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature10152
关键词
-
资金
- Howard Hughes Medical Institute Funding Source: Medline
- NHLBI NIH HHS [P01 HL103526] Funding Source: Medline
Transforming growth factor (TGF)-beta is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-beta 1 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-beta 1 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-beta 1 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据