Formation of helical hairpins during membrane protein integration into the endoplasmic reticulum membrane.: Role of the N and C-terminal flanking regions
Formation of helical hairpins during membrane protein integration into the endoplasmic reticulum membrane.: Role of the N and C-terminal flanking regions
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DOI：
10.1006/jmbi.2001.5108
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发表时间：
2001-11-09
影响因子：
5.6
通讯作者：
von Heijne, G
中科院分区：
文献类型：
--
作者：
Hermansson, M;Monné, M;von Heijne, G
螺旋发夹，两个紧密间隔的跨膜螺旋分开一个短的转折，是一种常见的结构元件在完整的膜蛋白。以前的研究螺旋发夹形成的序列决定因素集中在极性和带电残基的作用，放置在一个长的疏水残基的延伸集中，并产生了一个“倾向规模”的相对效率，不同的残基促进螺旋发夹的形成。在这项研究中，我们将注意力转移到带电残基侧翼的疏水伸展的作用。已知带电残基的簇阻碍膜易位，因此可以想象，侧接的带电残基可以迫使长的疏水片段形成螺旋发夹，即使在疏水段中没有或只有弱的促转残基。我们确实发现，赖氨酸，更令人惊讶的是，天冬氨酸残基强烈影响螺旋发夹的形成时，放置在旁边的聚亮氨酸为基础的跨膜段。我们还发现，一个簇的四个连续的赖氨酸残基可以影响螺旋发夹形成的效率，即使当放置类似于30个残基的疏水伸展下游。这些观察结果有有趣的影响，我们图片的方式膜蛋白拓扑结构的背景下，内质网（ER）的易位。(C)北京：科学出版社.
The helical hairpin, two closely spaced transmembrane helices separated by a short turn, is a common structural element in integral membrane proteins. Previous studies on the sequence determinants of helical hairpin formation have focussed on the role of polar and charged residues placed centrally in a long stretch of hydrophobic residues, and have yielded a "propensity scale" for the relative efficiency with which different residues promote the formation of helical hairpins. In this study, we shift our attention to the role of charged residues flanking the hydrophobic stretch. Clusters of charged residues are known to hinder membrane translocation, and thus flanking charged residues may conceivably force a long hydrophobic segment to form a helical hairpin even if there are no or only weakly turn-promoting residues in the hydrophobic stretch. We indeed find that Lys and, more surprisingly, Asp residues strongly affect helical hairpin formation when placed next to a poly-Leu-based transmembrane segment. We also find that a cluster of four consecutive Lys residues can affect the efficiency of helical hairpin formation even when placed similar to 30 residues downstream of the hydrophobic stretch. These observations have interesting implications for the way we picture membrane protein topogenesis within the context of the endoplasmic reticulum (ER) translocon. (C) 2001 Academic Press.