Disorder in a target for the Smad2 mad Homology 2 domain and its implications for binding and specificity
Disorder in a target for the Smad2 mad Homology 2 domain and its implications for binding and specificity
复制标题
DOI：
10.1074/jbc.m404375200
复制
发表时间：
2004-09-24
影响因子：
4.8
通讯作者：
Forman-Kay, JD
中科院分区：
文献类型：
--
作者：
Chong, PA;Ozdamar, B;Forman-Kay, JD
Smad2 Mad同源性2（MH2）结构域结合不共享共同序列基序的不同蛋白质组。我们已经使用NMR来研究这些相互作用的蛋白质之一，Smad受体激活（SARA）的Smad锚的Smad结合结构域（SBD）的结构。我们的研究结果表明，未结合的SBD是高度无序的，没有形成稳定的二级或三级结构。此外，我们已经使用荧光结合研究来研究MH2结构域和SBD之间的相互作用，并发现没有SBD的区域主导MH2和SBD之间的相互作用。我们的研究结果与MH2上一系列能够识别蛋白质无序区域的疏水补丁一致。这些发现阐明了一种机制，通过这种机制，一个单一的结构域（MH2）可以特异性地识别一组不同的蛋白质，这些蛋白质是不相关的序列，从而更清楚地了解MH2结构域如何在转化生长因子β信号通路中发挥作用，并提出了控制与MH2结构域相互作用的可能机制。
The Smad2 Mad homology 2 (MH2) domain binds to a diverse group of proteins which do not share a common sequence motif. We have used NMR to investigate the structure of one of these interacting proteins, the Smad binding domain (SBD) of Smad anchor for receptor activation ( SARA). Our results indicate that the unbound SBD is highly disordered and forms no stable secondary or tertiary structures. Additionally we have used fluorescence binding studies to study the interaction between the MH2 domain and SBD and find that no region of the SBD dominates the interaction between the MH2 and the SBD. Our results are consistent with a series of hydrophobic patches on the MH2 that are able to recognize disordered regions of proteins. These findings elucidate a mechanism by which a single domain (MH2) can specifically recognize a diverse set of proteins which are unrelated by sequence, lead to a clearer picture of how MH2 domains function in the transforming growth factor-beta-signaling pathway and suggest possible mechanisms for controlling interactions with MH2 domains.