Exploring the binding diversity of intrinsically disordered proteins involved in one-to-many binding
Exploring the binding diversity of intrinsically disordered proteins involved in one-to-many binding
复制标题
DOI：
10.1002/pro.2207
复制
发表时间：
2013-03-01
期刊：
影响因子：
8
通讯作者：
Dunker, A. Keith
中科院分区：
文献类型：
--
作者：
Hsu, Wei-Lun;Oldfield, Christopher J.;Dunker, A. Keith
分子识别特征（MoRFs）是一种内在无序的蛋白质区域，通过无序到有序的转变与伴侣结合。在一对多结合中，单个MoRF单独结合两个或更多个不同的伴侣。从蛋白质数据库收集基于MoRF的一对多蛋白质蛋白质相互作用（PPI）实例，产生与29个配偶体结合的23个MoRF，所有对相同的MoRF配偶体具有小于25%的序列同一性。其中，8个MoRF与29个具有完全不同折叠的配偶体结合，而15个MoRF与25个具有相同折叠但具有低序列同一性的配偶体结合。对于这两种类型的合作伙伴的变化，主链和侧链扭转角旋转，以带来所需的构象变化，使一个单一的MoRF和不同的合作伙伴之间的紧密配合。选择性剪接事件（ASES）和翻译后修饰（PTM）也被发现有助于不同的合作伙伴结合。由于ASES和PTM通常都发生在无序区域，并且由于ASES和PTM通常都是组织特异性的，因此这些数据表明MoRF，ASES和PTM可能会合作改变不同细胞类型中的PPI网络。这些数据扩大了一组仔细研究的MoRF，使用固有的灵活性，也使用基于ASE和/或PTM的表面修饰，使相同的无序段选择性地与两个或更多个合作伙伴。参与MoRFs及其通过ASE或PTM的修饰的少量残基可以简化信号网络多样性的进化性。
Molecular recognition features (MoRFs) are intrinsically disordered protein regions that bind to partners via disorder-to-order transitions. In one-to-many binding, a single MoRF binds to two or more different partners individually. MoRF-based one-to-many proteinprotein interaction (PPI) examples were collected from the Protein Data Bank, yielding 23 MoRFs bound to 29 partners, with all pairs of same-MoRF partners having less than 25% sequence identity. Of these, 8 MoRFs were bound to 29 partners having completely different folds, whereas 15 MoRFs were bound to 25 partners having the same folds but with low sequence identities. For both types of partner variation, backbone and side chain torsion angle rotations were used to bring about the conformational changes needed to enable close fits between a single MoRF and distinct partners. Alternative splicing events (ASEs) and posttranslational modifications (PTMs) were also found to contribute to distinct partner binding. Because ASEs and PTMs both commonly occur in disordered regions, and because both ASEs and PTMs are often tissue-specific, these data suggest that MoRFs, ASEs, and PTMs may collaborate to alter PPI networks in different cell types. These data enlarge the set of carefully studied MoRFs that use inherent flexibility and that also use ASE-based and/or PTM-based surface modifications to enable the same disordered segment to selectively associate with two or more partners. The small number of residues involved in MoRFs and in their modifications by ASEs or PTMs may simplify the evolvability of signaling network diversity.