Structural dynamics and regulation of the Sec61 complex

• Applicants: Professor Dr.-Ing. Richard Wagner; Professor Dr. Richard Zimmermann
• Subject Area: Biochemistry
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 50070218

The project is directed towards the mechanism and regulation of the central component of the machinery that is responsible for protein transport into the endoplasmic reticulum (ER), the Sec61 complex. After interaction with precursor polypeptides the mammalian and yeast Sec61 complexes transiently form a polypeptide- and ion-conducting channel. In order to limit calcium leakage from the ER at the level of the Sec61 complex, the mammalian Sec61 channel activities are structurally modulated by ribosomes, calmodulin (CaM), BiP, and, putatively, the Sec62/Sec63 complex. Future work will address the effect of CaM on channel properties of the yeast Sec61 complex as well as the role of ribosomes and ribosome/nascent chain complexes on the channel activities of mammalian and yeast Sec61 complexes. Furthermore, the native 3D organization of ER bound polysomes will be studied. In addition, the structure of the ribosome/CaM/Sec61 complex and the functional role of ribosome- and Sec61-binding of Sec62 will be characterized.

• DFG Programme: Research Units
• Subproject of: FOR 967: Functions and Mechanisms of Ribosomal Tunnel Exit Ligands (RTeLs)