Structural Biology and Evolution of the TGF-β Family.
Structural Biology and Evolution of the TGF-β Family.
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DOI：
10.1101/cshperspect.a022103
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发表时间：
2016-12-01
影响因子：
7.2
通讯作者：
Springer TA
中科院分区：
文献类型：
--
作者：
Hinck AP;Mueller TD;Springer TA
我们综述了转化生长因子β（TGF - β）家族成员、拮抗性或激动性调节剂以及在细胞外环境中调节TGF - β信号传导的受体的演化和结构。所有家族成员及其许多拮抗剂共有的生长因子（GF）结构域是从一个常见的胱氨酸结生长因子（CKGF）结构域演化而来的。CKGF超家族在原始后生动物中包含六个不同的家族，包括TGF - β和Dan家族。与同样决定体轴、细胞命运、组织的Wnt/卷曲蛋白（Frizzled）和Notch/Delta家族以及其他包含平行演化的CKGF结构域的家族相比，TGF - β家族在演化中是最富有成果的。TGF - β家族的前结构域和生长因子之间的复合物为通过从前臂闭合到前臂开放的前复合物构象转变来调节生长因子释放提出了一种新范式。细胞外信号传导最后一步的三元复合物展示了TGF - β生长因子二聚体如何结合细胞表面的I型和II型受体，并使我们能够理解细胞外信号传导中的许多特异性和混杂性。然而，结构表明当生长因子结合排斥性导向分子（RGM）家族共受体时，I型受体直到到达细胞内被膜包裹的区室才会结合，这模糊了细胞外和细胞内信号传导之间的界限。调节蛋白结构展示了包括卵泡抑素、头蛋白以及腱蛋白家族成员在内的结构多样的拮抗剂如何结合生长因子来调节信号传导；与Dan家族的复合物仍然难以捉摸。要理解这些分子成分如何在体内细胞外环境中组装形成信号传导枢纽，还需要大量的工作。
We review the evolution and structure of members of the transforming growth factor β (TGF-β) family, antagonistic or agonistic modulators, and receptors that regulate TGF-β signaling in extracellular environments. The growth factor (GF) domain common to all family members and many of their antagonists evolved from a common cystine knot growth factor (CKGF) domain. The CKGF superfamily comprises six distinct families in primitive metazoans, including the TGF-β and Dan families. Compared with Wnt/Frizzled and Notch/Delta families that also specify body axes, cell fate, tissues, and other families that contain CKGF domains that evolved in parallel, the TGF-β family was the most fruitful in evolution. Complexes between the prodomains and GFs of the TGF-β family suggest a new paradigm for regulating GF release by conversion from closed- to open-arm procomplex conformations. Ternary complexes of the final step in extracellular signaling show how TGF-β GF dimers bind type I and type II receptors on the cell surface, and enable understanding of much of the specificity and promiscuity in extracellular signaling. However, structures suggest that when GFs bind repulsive guidance molecule (RGM) family coreceptors, type I receptors do not bind until reaching an intracellular, membrane-enveloped compartment, blurring the line between extra- and intracellular signaling. Modulator protein structures show how structurally diverse antagonists including follistatins, noggin, and members of the chordin family bind GFs to regulate signaling; complexes with the Dan family remain elusive. Much work is needed to understand how these molecular components assemble to form signaling hubs in extracellular environments in vivo.
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影响因子：
3.7
作者：
Boschert V;van Dinther M;Weidauer S;van Pee K;Muth EM;Ten Dijke P;Mueller TD
通讯作者：
Mueller TD
影响因子：
3.5
作者：
BORK, P;SANDER, C
通讯作者：
SANDER, C
DOI：
10.1073/pnas.0602558103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Allendorph, George P.;Vale, Wylie W.;Choe, Senyon
通讯作者：
Choe, Senyon
影响因子：
5.7
作者：
Boesen, CC;Radaev, S;Sun, PD
通讯作者：
Sun, PD
影响因子：
64.8
作者：
Ashe, HL;Levine, M
通讯作者：
Levine, M