Prince Henry's Institute of Medical Research, 246 Clayton Road, Clayton, Vic 3168, Australia.
Mol Cell Endocrinol. 2012 Aug 15;359(1-2):2-12. doi: 10.1016/j.mce.2011.06.030. Epub 2011 Jul 8.
Like other members of the transforming growth factor-β (TGF-β) superfamily, activins are synthesised as precursor molecules comprising an N-terminal prodomain and C-terminal mature region. During synthesis, the prodomain interacts non-covalently with mature activin, maintaining the molecule in a conformation competent for dimerisation. Dimeric precursors are cleaved by proprotein convertases and activin is secreted from the cell non-covalently associated with its propeptide. Extracellularly, the propeptide interacts with heparan sulfate proteoglycans to regulate activin localization within tissues. The mature activin dimer exhibits the classic 'open-hand' structure of TGF-β ligands with 'finger-like' domains projecting outward from the cysteine knot core of the molecule. These finger domains form the binding epitopes for type I and II serine/threonine kinase receptors. Activins ability to access its signalling receptors is regulated by the extracellular binding proteins, follistatin, follistatin-like-3, and by inhibins, which, in the presence of betaglycan, sequester type II receptors.
像转化生长因子-β（TGF-β）超家族的其他成员一样，激活素是作为前体分子合成的，这些分子包括 N 端前导序列和 C 端成熟区域。在合成过程中，前导序列与成熟的激活素非共价相互作用，使分子保持二聚化的构象。前体分子被蛋白原转化酶切割，激活素从细胞中分泌出来，与它的前肽非共价结合。在细胞外，前肽与硫酸乙酰肝素蛋白聚糖相互作用，调节激活素在组织中的定位。成熟的激活素二聚体表现出经典的“张开的手”结构，TGF-β 配体的“指状”结构从分子的半胱氨酸结核心向外突出。这些指状结构形成了 I 型和 II 型丝氨酸/苏氨酸激酶受体的结合表位。激活素能够与信号受体相互作用的能力受到细胞外结合蛋白、卵泡抑素、卵泡抑素样 3 和抑制素的调节，这些蛋白在β聚糖存在的情况下，将 II 型受体隔离。
