Division of Molecular Structural Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Tomtebodavägen 6, 4tr, Stockholm S-171 77, Sweden.
J Mol Biol. 2013 Jun 26;425(12):2208-18. doi: 10.1016/j.jmb.2013.03.024. Epub 2013 Mar 21.
Erv41p is a conserved integral membrane protein that is known to play a role in transport between the endoplasmic reticulum and Golgi apparatus, part of the early secretory pathway of eukaryotes. However, the exact function of the protein is not known, and it shares very low sequence identity with proteins of known structure or function. Here we present the structure of the full lumenal domain of Erv41p from Saccharomyces cerevisiae, determined by X-ray crystallography to a resolution of 2.0Å. The structure reveals the protein to be composed predominantly of two large β-sheets that form a twisted β-sandwich. Comparison to structures in the Protein Data Bank shows that the Erv41p lumenal domain displays only limited similarity to β-sandwich domains of other proteins. Analysis of the surface properties of the protein identifies an extensive patch of negative electrostatic potential on the exposed surface of one of the β-sheets, which likely forms a binding site for a ligand or interaction partner. A predominantly hydrophobic region close to the membrane interface is identified as a likely site for protein-protein interaction. This structure, the first of Erv41p or any of its homologues, provides a new starting point for studies of the roles of Erv41p and its interaction partners in the eukaryotic secretory pathway.
Erv41p 是一种保守的整合膜蛋白，已知在真核生物早期分泌途径中内质网和高尔基体之间的运输中发挥作用。然而，该蛋白的确切功能尚不清楚，并且与已知结构或功能的蛋白的序列同一性非常低。在这里，我们通过 X 射线晶体学确定了酿酒酵母 Erv41p 的完整腔域结构，分辨率为 2.0Å。该结构表明该蛋白主要由两个大的β-sheet 组成，形成扭曲的β-sandwich。与蛋白质数据库中的结构比较表明，Erv41p 腔域与其他蛋白的β-sandwich 结构域仅具有有限的相似性。对蛋白表面特性的分析表明，在其中一个β-sheet 的暴露表面上存在广泛的负静电势区域，该区域可能形成配体或相互作用伙伴的结合位点。靠近膜界面的主要疏水区被确定为蛋白-蛋白相互作用的可能位点。该结构是 Erv41p 或其任何同源物的第一个结构，为研究 Erv41p 及其相互作用伙伴在真核生物分泌途径中的作用提供了新的起点。
