Residues in substrate proteins that interact witn GroEL in tne capture process are buried in the native state
Residues in substrate proteins that interact witn GroEL in tne capture process are buried in the native state
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DOI：
10.1073/pnas.0600433103
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发表时间：
2006-03-21
影响因子：
11.1
通讯作者：
Thirumalai, D
中科院分区：
文献类型：
--
作者：
Stan, G;Brooks, BR;Thirumalai, D
我们使用生物信息学方法根据两个简单的标准来预测大肠杆菌伴侣蛋白 GroEL 的天然底物蛋白。天然底物蛋白应含有与 GroES 的移动环肽序列相似的结合基序，该环肽在伴侣蛋白循环期间取代结合基序。其次，每个底物蛋白应包含多个拷贝的结合基序，以便伴侣蛋白可以对底物蛋白进行“工作”。为了验证这些标准，我们使用了 252 种蛋白质的数据库，这些蛋白质已被实验证明与体内伴侣蛋白机制相互作用。超过 80% 的人是通过这些标准来识别的。数据库中所有 79 种具有已知三维结构的蛋白质的结合基序均以天然状态被隐藏（< 50% 溶剂可及表面积）。我们的结果表明，结合基序在天然状态下是不可接近的，但在未折叠状态下会暴露在溶剂中，从而使 GroEL 能够区分未折叠状态和天然状态。底物蛋白天然状态下的结合基序的结构包括α螺旋、β链和无规卷曲。二级结构的多样性意味着识别基序被 GroES 的移动环置换后，存在大量且多样的构象转变。
We have used a bioinformatic approach to predict the natural substrate proteins for the Escherichia coli chaperonin GroEL based on two simple criteria. Natural substrate proteins should contain binding motifs similar in sequence to the mobile loop peptide of GroES that displaces the binding motif during the chaperonin cycle. Secondly, each substrate protein should contain multiple copies of the binding motif so that the chaperonin can perform "work" on the substrate protein. To validate these criteria, we have used a database of 252 proteins that have been experimentally shown to interact with the chaperonin machinery in vivo. More than 80% are identified by these criteria. The binding motifs of all 79 proteins in the database with a known three-dimensional structure are buried (< 50% solvent-accessible surface area) in the native state. Our results show that the binding motifs are inaccessible in the native state but become solvent-exposed in unfolded state, thus enabling GroEL to distinguish between unfolded and native states. The structures of the binding motif in the native states of the substrate proteins include alpha-helices, beta-strands, and random coils. The diversity of secondary structures implies that there are large and varied conformational transitions in the recognition motifs after their displacement by the mobile loops of GroES.