Is Asp-His-Ser/Thr-Trp tetrad hydrogen-bond network important to WD4O-repeat proteins: A statistical and theoretical study
Is Asp-His-Ser/Thr-Trp tetrad hydrogen-bond network important to WD4O-repeat proteins: A statistical and theoretical study
复制标题
Asp-His-Ser/Thr-Trp 四分体氢键网络对 WD4O 重复蛋白是否重要：统计和理论研究
DOI：
10.1002/prot.22638
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发表时间：
2010-04-01
影响因子：
2.9
通讯作者：
Wu, Yun-Dong
中科院分区：
文献类型：
--
作者：
Wu, Xian-Hui;Zhang, Hui;Wu, Yun-Dong
WD 40-repeat蛋白是一种丰富的蛋白质，在形成蛋白质复合物中起重要作用。该结构域通常具有七个WD 40重复，其折叠成七个β折叠螺旋桨，每个β折叠在四链结构中。对蛋白质数据库中20个WD 40重复序列蛋白质的分析表明，每个蛋白质都至少有一个Asp-His-Ser/Thr-Trp（D-H-S/T-W）氢键四联体，有些蛋白质甚至有6 ~ 7个这样的四联体。四分体中四个残基的相对位置也是保守的。对560个人WD 40重复蛋白序列的序列比对分析显示，它们具有非常相似的特征，表明这种四分体可能是WD 40重复蛋白的一个普遍特征。我们进行了密度泛函理论，发现这些四联体可以导致显着的稳定性，包括氢键的协同性。涉及Trp的氢键是重要的。这些结果使我们提出，四分体可能是至关重要的稳定性和折叠的这些蛋白质的机制。
WD40-repeat proteins are abundant and play important roles in forming protein complexes. The domain usually has seven WD40 repeats, which folds into a seven beta-sheet propeller with each beta-sheet in a four-strand structure. An analysis of 20 available WD40-repeat proteins in Protein Data Bank reveals that each protein has at least one Asp-His-Ser/Thr-Trp (D-H-S/T-W) hydrogen-bonded tetrad, and some proteins have up to six or seven such tetrads. The relative positions of the four residues in the tetrads are also found to be conserved. A sequence alignment analysis of 560 WD40-repeat protein sequences in human reveals very similar features, indicating that such tetrad may be a general feature of WD40-repeat proteins. We carried out density functional theory and found that these tetrads can lead to significant stabilization including hydrogen-bonding cooperativity. The hydrogen bond involving Trp is significant. These results lead us to propose that the tetrads may be critical to the stability and the mechanism of folding of these proteins.