Transmembrane glycine zippers: Physiological and pathological roles in membrane proteins
Transmembrane glycine zippers: Physiological and pathological roles in membrane proteins
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DOI：
10.1073/pnas.0501234102
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发表时间：
2005-10-04
影响因子：
11.1
通讯作者：
Bowie, JU
中科院分区：
文献类型：
--
作者：
Kim, S;Jeon, TJ;Bowie, JU
我们在膜蛋白中观察到一个共同的序列基序，我们称之为甘氨酸拉链。甘氨酸拉链基序在膜蛋白序列中被过度代表和保守，在许多情况下，甘氨酸拉链基序的突变对功能有害。甘氨酸拉链具有显著的结构影响，产生强大的驱动力右手包装对邻近的螺旋。因此，甘氨酸拉链基序的存在直接导致可测试的结构假设，特别是对于形成通道的甘氨酸拉链蛋白亚类。例如，我们认为β淀粉样肽在体外形成的膜孔是通过甘氨酸拉链包装构建的，并发现甘氨酸拉链基序的突变阻碍了通道的形成。我们的研究结果强调了在各种正常和病理过程中一个重要的结构基序。
We have observed a common sequence motif in membrane proteins, which we call a glycine zipper. Glycine zipper motifs are strongly overrepresented and conserved in membrane protein sequences, and mutations in glycine zipper motifs are deleterious to function in many cases. The glycine zipper has a significant structural impact, engendering a strong driving force for right-handed packing against a neighboring helix. Thus, the presence of a glycine zipper motif leads directly to testable structural hypotheses, particularly for a subclass of glycine zipper proteins that form channels. For example, we suggest that the membrane pores formed by the amyloid-beta peptide in vitro are constructed by glycine zipper packing and find that mutations in the glycine zipper motif block channel formation. Our findings highlight an important structural motif in a wide variety of normal and pathological processes.