Transmembrane domains are critical to the interaction between platelet glycoprotein V and glycoprotein Ib-IX complex.
Transmembrane domains are critical to the interaction between platelet glycoprotein V and glycoprotein Ib-IX complex.
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跨膜结构域对于血小板糖蛋白 V 和糖蛋白 Ib-IX 复合物之间的相互作用至关重要。
DOI：
10.1111/j.1538-7836.2012.04841.x
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发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Mo X;Liu L;López JA;Li R
血小板表面的血管性血友病因子受体（vonWillebrand factor receptor，GP）Ib-IX-V复合物与止血和血栓形成密切相关。GPV亚基与GPIb-IX相互作用形成GPIb-IX-V复合物，但其分子基础尚不清楚。先前观察到GPV在质膜中的有效表达需要GPIb-IX的共表达。假设GPIb-IX通过直接相互作用稳定GPV，从而增强GPV表面表达，我们的目的是在这项研究中，以确定介导GPV和GPIb-IX之间的相互作用的复杂结构元件，通过分析突变对GPV的转染中国仓鼠卵巢细胞表面表达的影响。GPIb-IX增强GPV表面表达需要GPV和GPIbα的跨膜结构域，因为用不相关的多聚亮氨酸-丙氨酸序列取代GPV跨膜结构域消除了GPIb-IX的增强作用。GPV跨膜螺旋的额外诱变分析鉴定了含有保守极性残基的三个螺旋侧对于有效GPV表面表达至关重要。类似地，将GPIbα跨膜结构域的三侧残基（Gly 495/Ala 502/Leu 509、Phe 491/Trp 498/Val 505和Y 492/L499/L506）替换为亮氨酸保留了GPIb-IX的表面表达水平，但显著改变了GPV的表面表达水平。我们的研究结果首次证明了GPV跨膜结构域对GPV有效表面表达的重要性，并表明GPV和GPIbα跨膜结构域相互作用，有助于GPIb-IX-V复合物的组装。
The glycoprotein (GP) Ib-IX-V complex, the von Willebrand factor receptor on platelet surface, is critically involved in hemostasis and thrombosis. GPV subunit interacts with GPIb-IX to form the GPIb-IX-V complex, but the underlying molecular basis remains unclear. It was observed earlier that efficient expression of GPV in the plasma membrane requires coexpression of GPIb-IX. Hypothesizing that GPIb-IX stabilizes GPV through direct interaction and consequently enhances GPV surface expression, we aim in this study to identify structural elements in the complex that mediate the interaction between GPV and GPIb-IX by analyzing mutational effects on GPV surface expression in transfected Chinese hamster ovary cells. Enhancement of GPV surface expression by GPIb-IX requires transmembrane domains of both GPV and GPIbα, as replacing GPV transmembrane domain with an unrelated poly-leucine-alanine sequence abolished the enhancing effect of GPIb-IX. Additional mutagenesis analysis of the GPV transmembrane helix identified three helical sides containing conserved polar residues as critical to efficient GPV surface expression. Similarly, replacing residues in three sides (Gly495/Ala502/Leu509, Phe491/Trp498/Val505, and Y492/L499/L506) of the GPIbα transmembrane domain to leucines preserved the surface expression level of GPIb-IX but significantly altered that of GPV. Our results demonstrate for the first time the importance of transmembrane domains to efficient surface expression of GPV and suggest that GPV and GPIbα transmembrane domains interact with each other, contributing to assembly of the GPIb-IX-V complex.
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影响因子：
9.8
作者：
Feng J;Call ME;Wucherpfennig KW
通讯作者：
Wucherpfennig KW
分析使用重构的哺乳动物细胞表达模型，对整联蛋白α（IIB）β（3）的血小板糖蛋白IB-IX介导的激活的作用分析。
影响因子：
7.8
作者：
Gu, M;Xi, X;Englund, G D;Berndt, M C;Du, X
通讯作者：
Du, X
影响因子：
4.8
作者：
Bodnar, RJ;Xi, XD;Du, XP
通讯作者：
Du, XP
DOI：
10.1016/s1357-2725(02)00280-7
发表时间：
2003-08-01
影响因子：
4
作者：
Andrews, RK;Gardiner, EE;Berndt, MC
通讯作者：
Berndt, MC
影响因子：
6.7
作者：
Andrews, RK;Shen, Y;Berndt, MC
通讯作者：
Berndt, MC