Motifs of serine and threonine can drive association of transmembrane helices
Motifs of serine and threonine can drive association of transmembrane helices
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DOI：
10.1006/jmbi.2001.5353
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发表时间：
2002-02-22
影响因子：
5.6
通讯作者：
Engelman, DM
中科院分区：
文献类型：
--
作者：
Dawson, JP;Weinger, JS;Engelman, DM
已知的含有关键甘氨酸残基的序列基序可以驱动跨膜螺旋的同源齐聚。为了寻找其他基序，我们建立了一个随机的跨膜界面文库，其中省略了甘氨酸。用TOXCAT系统检测大肠杆菌内膜的跨膜螺旋结合，从文库中筛选出高亲和力的同源齐聚序列。出现频率最高的两个基序是SxxSSxxT和SxxxSSxxT。丝氨酸和苏氨酸残基中的任何一个等位突变为非极性残基，消除了寡聚作用，表明这些位置之间的相互作用是特异的，需要扩展的丝氨酸和苏氨酸羟基基序。对这些序列的计算机模拟产生了几个化学上可信的结构，这些结构包含丝氨酸和苏氨酸残基之间的多个氢键。虽然单丝氨酸或苏氨酸侧链似乎不能促进螺旋结合，但基序可以通过螺旋间氢键的合作网络来驱动强烈和特定的结合。(C)2002年爱思唯尔科学有限公司。
Known sequence motifs containing key glycine residues can drive the homo-oligomerization of transmembrane helices. To find other motifs, a randomized library of transmembrane interfaces was generated in which glycine was omitted. The TOXCAT system, which measures transmembrane helix association in the Escherichia coli inner membrane, was used to select high-affinity homo-oligomerizing sequences in this library. The two most frequently occurring motifs were SxxSSxxT and SxxxSSxxT. Isosteric mutations of any one of the serine and threonine residues to non-polar residues abolished oligomerization, indicating that the interaction between these positions is specific and requires an extended motif of serine and threonine hydroxyl groups. Computational modeling of these sequences produced several chemically plausible structures that contain multiple hydrogen bonds between the serine and threonine residues. While single serine or threonine side-chains do not appear to promote helix association, motifs can drive strong and specific association through a cooperative network of interhelical hydrogen bonds. (C) 2002 Elsevier Science Ltd.