Structured States of Disordered Proteins from Genomic Sequences.
Structured States of Disordered Proteins from Genomic Sequences.
复制标题
DOI：
10.1016/j.cell.2016.09.010
复制
发表时间：
2016-09-22
期刊：
影响因子：
64.5
通讯作者：
Marks DS
中科院分区：
文献类型：
--
作者：
Toth-Petroczy A;Palmedo P;Ingraham J;Hopf TA;Berger B;Sander C;Marks DS
蛋白质的灵活性范围从简单的铰链运动到功能紊乱。大约一半的人类蛋白质含有明显的无序区域，几乎没有3D或功能信息，其中许多蛋白质与疾病有关。在先前成功预测有序蛋白质和RNA三维状态的进化耦合方法的基础上，我们开发了一种方法，可以用足够丰富的进化信息预测所有明显无序蛋白质的有序状态。该方法是高度准确的（79%）残基相互作用测试超过60个已知的无序区域捕获在绑定或特定条件。对人类蛋白质超过1000个明显无序区域的结构潜力进行评估，揭示了至少50%的结构有序连续体具有三维或二维状态的明显倾向。共同进化约束揭示了迄今为止在明显无序的蛋白质中未见的功能重要性结构。序列共变异揭示了柔性蛋白和无序蛋白的结构状态
Protein flexibility ranges from simple hinge movements to functional disorder. Around half of all human proteins contain apparently disordered regions, with little 3D or functional information, and many of these proteins are associated with disease. Building on the evolutionary couplings approach previously successful in predicting 3D states of ordered proteins and RNA, we developed a method to predict the potential for ordered states for all apparently disordered proteins with sufficiently rich evolutionary information. The approach is highly accurate (79%) for residue interactions as tested in over 60 known disordered regions captured in a bound or specific condition. Assessing the potential for structure of over 1000 apparently-disordered regions of human proteins reveals a continuum of structural order with at least 50% with clear propensity for three- or two-dimensional states. Co-evolutionary constraints reveal hitherto unseen structure of functional importance in apparently disordered proteins. Sequence co-variation shines a light on structural states in flexible and disordered proteins