Get4/Get5 复合物的结构特征及其与 Get3 的相互作用。
Structural characterization of the Get4/Get5 complex and its interaction with Get3.
机构信息
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
出版信息
Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12127-32. doi: 10.1073/pnas.1006036107. Epub 2010 Jun 16.
Abstract
The recently elucidated Get proteins are responsible for the targeted delivery of the majority of tail-anchored (TA) proteins to the endoplasmic reticulum. Get4 and Get5 have been identified in the early steps of the pathway mediating TA substrate delivery to the cytoplasmic targeting factor Get3. Here we report a crystal structure of Get4 and an N-terminal fragment of Get5 from Saccharomyces cerevisae. We show Get4 and Get5 (Get4/5) form an intimate complex that exists as a dimer (two copies of Get4/5) mediated by the C-terminus of Get5. We further demonstrate that Get3 specifically binds to a conserved surface on Get4 in a nucleotide dependent manner. This work provides further evidence for a model in which Get4/5 operates upstream of Get3 and mediates the specific delivery of a TA substrate.
摘要
最近阐明的 Get 蛋白负责将大多数尾部锚定（TA）蛋白靶向递送至内质网。Get4 和 Get5 已在介导 TA 底物递送至细胞质靶向因子 Get3 的途径的早期步骤中被鉴定出来。在这里，我们报道了来自酿酒酵母的 Get4 和 Get5 的 N 端片段的晶体结构。我们表明 Get4 和 Get5（Get4/5）形成紧密的复合物，该复合物以 Get5 的 C 末端介导的二聚体（两个 Get4/5 拷贝）形式存在。我们进一步证明 Get3 以核苷酸依赖的方式特异性结合到 Get4 上的保守表面上。这项工作为 Get4/5 在前 Get3 上运作并介导 TA 底物的特异性递送的模型提供了进一步的证据。
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1
The structure of Get4 reveals an alpha-solenoid fold adapted for multiple interactions in tail-anchored protein biogenesis.
FEBS Lett. 2010 Apr 16;584(8):1509-14. doi: 10.1016/j.febslet.2010.02.070. Epub 2010 Mar 3.
2
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J Biol Chem. 2010 Mar 26;285(13):9962-9970. doi: 10.1074/jbc.M109.087098. Epub 2010 Jan 27.
3
The genetic landscape of a cell.
Science. 2010 Jan 22;327(5964):425-31. doi: 10.1126/science.1180823.
4
Structural insight into the membrane insertion of tail-anchored proteins by Get3.
Genes Cells. 2010 Jan;15(1):29-41. doi: 10.1111/j.1365-2443.2009.01362.x. Epub 2009 Dec 15.
5
The crystal structures of yeast Get3 suggest a mechanism for tail-anchored protein membrane insertion.
PLoS One. 2009 Nov 30;4(11):e8061. doi: 10.1371/journal.pone.0008061.
6
Structural insights into tail-anchored protein binding and membrane insertion by Get3.
Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21131-6. doi: 10.1073/pnas.0910223106. Epub 2009 Nov 30.
7
Biogenesis of tail-anchored proteins: the beginning for the end?
J Cell Sci. 2009 Oct 15;122(Pt 20):3605-12. doi: 10.1242/jcs.041210.
8
Model for eukaryotic tail-anchored protein binding based on the structure of Get3.
Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14849-54. doi: 10.1073/pnas.0907522106. Epub 2009 Aug 14.
9
The structural basis of tail-anchored membrane protein recognition by Get3.
Nature. 2009 Sep 17;461(7262):361-6. doi: 10.1038/nature08319. Epub 2009 Aug 12.
10
Genomewide analysis reveals novel pathways affecting endoplasmic reticulum homeostasis, protein modification and quality control.
Genetics. 2009 Jul;182(3):757-69. doi: 10.1534/genetics.109.101105. Epub 2009 May 11.
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