Characterization of molecular recognition features, MoRFs, and their binding partners
Characterization of molecular recognition features, MoRFs, and their binding partners
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DOI：
10.1021/pr0701411
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Dunker, A. Keith
中科院分区：
文献类型：
--
作者：
Vacic, Vladimir;Oldfield, Christopher J.;Dunker, A. Keith
分子识别特征（MoRFs）是蛋白质无序的短的、易于相互作用的片段，其在特异性结合时经历无序到有序的转变，代表了表现出分子识别和结合功能的特定类别的固有无序区域。MoRF在各种蛋白质组中很常见，并且占据独特的结构和功能小生境，其中功能是内在紊乱的直接结果。从蛋白质数据库（PDB）收集的示例性MoRF已根据它们在结合状态下的结构分为三种亚型：α-MoRF形成R-螺旋，β-MoRF形成β-链，并且α-MoRF形成没有规则骨架氢键模式的结构。这些示例性MoRF在不存在其结合配偶体的情况下通过几个标准被指示为本质上无序的。在这项研究中，我们使用了几个几何和物理化学标准来检查62 α，20 β，和176 iota-MoRF复合物结构的性能。界面残基进行了检查，通过计算复杂的和孤立的单体之间的可及表面积的差异。将MoRF和MoRF伴侣界面残基的组成和理化性质与同二聚体、异二聚体和抗原-抗体复合物的界面残基进行比较。我们的分析表明，有显着差异的残留物的组成和几个几何和物理化学性质，可用于区分，具有高度的准确性，在蛋白质相互作用数据集的各种接口之间。这些研究结果的发展的MORF合作伙伴的相互作用预测的影响进行了讨论。此外，对于几个说明性实施例，检查了MoRF-伴侣复合物形成后的结构变化。
Molecular Recognition Features ( MoRFs) are short, interaction-prone segments of protein disorder that undergo disorder-to-order transitions upon specific binding, representing a specific class of intrinsically disordered regions that exhibit molecular recognition and binding functions. MoRFs are common in various proteomes and occupy a unique structural and functional niche in which function is a direct consequence of intrinsic disorder. Example MoRFs collected from the Protein Data Bank (PDB) have been divided into three subtypes according to their structures in the bound state: alpha-MoRFs form R-helices, beta-MoRFs form, beta-strands, and alpha-MoRFs form structures without a regular pattern of backbone hydrogen bonds. These example MoRFs were indicated to be intrinsically disordered in the absence of their binding partners by several criteria. In this study, we used several geometric and physiochemical criteria to examine the properties of 62 alpha-, 20 beta-, and 176 iota-MoRF complex structures. Interface residues were examined by calculating differences in accessible surface area between the complex and isolated monomers. The compositions and physiochemical properties of MoRF and MoRF partner interface residues were compared to the interface residues of homodimers, heterodimers, and antigen-antibody complexes. Our analysis indicates that there are significant differences in residue composition and several geometric and physicochemical properties that can be used to discriminate, with a high degree of accuracy, between various interfaces in protein interaction data sets. Implications of these findings for the development of MoRF-partner interaction predictors are discussed. In addition, structural changes upon MoRF-to-partner complex formation were examined for several illustrative examples.