Project Details
Projekt
Functional characterization of the ribosomal tunnel exit ligand ERj1
Subject Area
Biochemistry
Term
from 2008 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 50070218
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.
DFG Programme
Research Units
Participating Person
Professor Dr. Richard Zimmermann
