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首页> 外文期刊>Biochemistry >Structural Homology Discloses a Bifunctional Structural Motif at the N-Termini of G_alpha Proteins
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Structural Homology Discloses a Bifunctional Structural Motif at the N-Termini of G_alpha Proteins

机译：结构同源性揭示了G_alpha蛋白N末端的双功能结构基序

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摘要

In a family of proteins, often the three-dimensional structure has been experimentally determined only for one member or a few members of the family. Homology modeling can be used to model the structures of all other members of the family and thus allow comparision of these structures. This approach was applied to heterotrimeric G proteins that require anchorage to the plasma membrane to properly interact with membrane-bound receptors and downstream effectors. Lipid modification by palmitoylation is a fundamental contributor to this localization, but the signals leading to this modification are still unknown. In this work, homology models of all the different human G_alpha paralogs were generated using automated homology modeling, and the electrostatic potential of these proteins was calculated and visualized. This approach identifies a basic, positively charged, structural motif in the N-termini of heterotrimeric G proteins, which is not readily discernible from sequence alone. The basic motif is much reduced in those G_alpha subunits that also undergo myristoylation, suggesting that the basic patches and myristoylation play overlapping roles. These motifs can affect both membrane affinity and orientation and determine the palmitoylation of G_alpha subunits in cooperation with the G_(beta gamma) subunits, as has been corroborated by previous experimental stuides. Furthermore, other palmitoylated proteins such as GAP-43 and RGS proteins share this alpha-helical basic motif in their N-terminus. It therefore appears that this structural motif is more widely applicable as a membrane-targeting and palmitoylation-determining signal. The work presented hwere highights the possibilities available for experimentalists to discover structural motifs that are not readily observed by analysis of the linear sequence.
机译：在蛋白质家族中，通常仅通过实验确定了该家族的一个成员或几个成员的三维结构。同源建模可用于对家族中所有其他成员的结构进行建模，从而可以比较这些结构。该方法应用于需要锚定在质膜上才能与膜结合受体和下游效应子正确相互作用的异三聚体G蛋白。通过棕榈酰化作用进行的脂质修饰是该定位的根本原因，但是导致这种修饰的信号仍然未知。在这项工作中，使用自动同源性建模生成了所有不同人类G_alpha旁系同源物的同源性模型，并对这些蛋白质的静电势进行了计算和可视化。这种方法在异三聚体G蛋白的N末端鉴定出一个基本的，带正电荷的结构基序，这很难从单独的序列中辨别出来。在也经历肉豆蔻酰基化的G_alpha亚基中，基本基序大大减少，这表明基本斑块和肉豆蔻酰基化起重叠作用。如先前的实验研究所证实的，这些基序可以影响膜亲和力和方向，并确定G_alpha亚基与G_ββ亚基协同作用的棕榈酰化。此外，其他棕榈酰化的蛋白质（例如GAP-43和RGS蛋白质）在其N末端共享此alpha螺旋基本基序。因此似乎该结构基序更广泛地用作膜靶向和棕榈酰化确定信号。提出的工作给实验者提供了发现通过线性序列分析不容易发现的结构基序的可能性。

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