Functional characterization of the ribosomal tunnel exit ligand ERj1

核糖体隧道出口配体 ERj1 的功能表征

• 批准号: 64346011
• 负责人: Professor Dr. Roland Beckmann
• 金额: --
• 依托单位: Genzentrum - Laboratorium für molekulare Biologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/64346011?language=en
• 关键词: Functional; characterization; ribosomal; tunnel; exit

ERj1 is a membrane-resident Hsp40 chaperon of the endoplasmic reticulum (ER), which recruits the ER-lumenal Hsp70 chaperon, BiP via the ER membrane to translating ribosomes. Furthermore, ERj1 modulates the translational activity of ribosomes by blocking initiation in the absence of BiP. In addition, ERj1 was characterized as potential transcription factor. We identified a nonapeptide within the cytosolic domain of ERj1 as responsible for ribosome interaction and characterized it as the modulator of translation activity. At the level of the ribosome, rRNA was shown to be involved in binding of ERj1 and the exit site of the ribosome was identified as the interacting site by biochemistry and Cryo-EM. Thus, the modulation of translation involves an allosteric mechanism, apparently mediated by conformational changes in the ribosome. Since ERj1 simultaneously binds to both, the ribosome and BiP, it is predestined to be involved in the process of protein transport into the ER. Furthermore, we postulate that ER1 plays a dual role in the regulation of gene expression – at the level of transcription as well as translation. The aim of our project is to elucidate the function(s) of ERj1, ultimately at the atomic level. In these studies quantitative aspects in comparison to the other ribosomal ligands (NAC, RAC, Sec61 complex) will also be addressed.

ERj 1是内质网（ER）的膜驻留Hsp 40伴侣，其通过ER膜将ER内腔的Hsp 70伴侣BiP募集到翻译核糖体。此外，ERj 1通过在BiP不存在的情况下阻断起始来调节核糖体的翻译活性。另外，ERj 1是一个潜在的转录因子。我们确定了一个九肽内ERj 1的胞质结构域负责核糖体相互作用，其特点是作为翻译活性的调节剂。在核糖体水平，rRNA被证明参与ERj 1的结合，并且核糖体的出口位点被鉴定为通过生化和Cryo-EM的相互作用位点。因此，翻译的调节涉及变构机制，显然是由核糖体的构象变化介导的。由于ERj 1同时与核糖体和BiP结合，因此它注定参与蛋白质转运到ER中的过程。此外，我们假设ER 1在基因表达的调节中起双重作用-在转录和翻译水平上。我们项目的目的是阐明ERj 1的功能，最终在原子水平上。在这些研究中，与其他核糖体配体（NAC，RAC，Sec 61复合物）相比，定量方面也将得到解决。

项目成果

Evolutionary gain of function for the ER membrane protein Sec62 from yeast to humans.

• DOI: 10.1091/mbc.e09-08-0730
• 发表时间: 2010-03-01
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Müller L;de Escauriaza MD;Lajoie P;Theis M;Jung M;Müller A;Burgard C;Greiner M;Snapp EL;Dudek J;Zimmermann R
• 通讯作者: Zimmermann R

Sec62 Protein Level is Crucial for the ER Stress Tolerance of Prostate Cancer

• DOI: 10.1002/pros.21324
• 发表时间: 2011-07-01
• 期刊: PROSTATE
• 影响因子: 2.8
• 作者: Greiner, Markus;Kreutzer, Birgit;Wullich, Bernd
• 通讯作者: Wullich, Bernd

Proteomic insights into non-small cell lung cancer: New ideas for cancer diagnosis and therapy from a functional viewpoint

非小细胞肺癌的蛋白质组学见解：从功能角度进行癌症诊断和治疗的新思路

• DOI: 10.1016/j.euprot.2014.05.004
• 发表时间: 2014
• 期刊: Eupa Open Proteomics
• 作者: Linxweiler;Zahedi;Kollipara;Zimmermann;Greiner
• 通讯作者: Greiner

Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria

• DOI: 10.1038/emboj.2013.46
• 发表时间: 2013-04-03
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Pfeiffer, Natalie V.;Dirndorfer, Daniela;Tatzelt, Joerg
• 通讯作者: Tatzelt, Joerg

TRC40 can deliver short secretory proteins to the Sec61 translocon.

• DOI: 10.1242/jcs.102608
• 发表时间: 2012-08-01
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Johnson N;Vilardi F;Lang S;Leznicki P;Zimmermann R;High S
• 通讯作者: High S