Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada.
Structure. 2013 Mar 5;21(3):332-41. doi: 10.1016/j.str.2012.12.013. Epub 2013 Jan 31.
Autoinhibition plays a significant role in the regulation of many proteins. By analyzing autoinhibited proteins, we demonstrate that these proteins are enriched in intrinsic disorder because of the properties of their inhibitory modules (IMs). A comparison of autoinhibited proteins with structured and intrinsically disordered IMs revealed that in the latter group (1) multiple phosphorylation sites are highly abundant; (2) splice variants occur in greater number than in their structured cousins; and (3) activation is often associated with changes in secondary structure in the IM. Analyses of families of autoinhibited proteins revealed that the levels of disorder in IMs can vary significantly throughout homologous proteins, whereas residues located at the interfaces between the IMs and inhibited domains are conserved. Our findings suggest that intrinsically disordered IMs provide advantages over structured ones that are likely to be exploited in the fine-tuning of the equilibrium between active and inactive states of autoinhibited proteins.
自动抑制在许多蛋白质的调节中起着重要作用。通过分析自动抑制蛋白，我们证明这些蛋白由于其抑制模块 (IM) 的特性而富含内在无序性。将自动抑制蛋白与结构和内在无序的 IM 进行比较表明，在后一组中：（1）存在高度丰富的多个磷酸化位点；（2）剪接变体的数量比其结构同源物更多；（3）激活通常与 IM 中二级结构的变化相关联。对自动抑制蛋白家族的分析表明，IM 中的无序程度在同源蛋白中可能有很大差异，而位于 IM 和受抑制结构域之间界面的残基是保守的。我们的发现表明，与结构 IM 相比，内在无序的 IM 具有优势，这可能在自动抑制蛋白的活性和非活性状态之间的平衡的微调中得到利用。
