Active modes of the translocon

Gogala, Marko (2015): Active modes of the translocon: snapshots of Sec61 interactions with different substrates and co-factors. Dissertation, LMU München: Faculty of Chemistry and Pharmacy

Abstract

All proteins are synthesized in the cytoplasm. However some proteins function outside of cells, in the cell membrane, in the endoplasmic reticulum or one of the connected vesicular systems and need to be sorted and accordingly transported. Consequently, the secretory pathway, a highly conserved protein targeting, translocation and membrane insertion system has evolved to cope with this task. The central actor in the secretory pathway is the heterotrimeric Sec61αβγ protein complex also known as the translocon. This protein complex has been shown to act as a transmembrane channel facilitating protein translocation into the lumen of the endoplasmic reticulum, a starting point in protein secretion. The complex also contains a lateral opening, termed ‘lateral gate’ through which proteins have been suggested to insert into the membrane of the endoplasmic reticulum. The mechanics of translocon opening for protein secretion or membrane insertion has been a matter of debate. The results presented here show secondary structure level resolution cryo-electron microscopic structures of the translocon in complex with stalled ribosome-nascent chain complexes carrying substrates with propensity for either secretion or membrane insertion as well as ribosome-bound inactive translocon molecules. The observed differences in secondary structure suggest a model for translocon activity in protein sorting.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Protein secretion, membrane insertion, trans-membrane proteins, Sec61, OST, glycosylation
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 540 Chemistry and allied sciences
• Faculties: Faculty of Chemistry and Pharmacy
• Language: English
• Date of oral examination: 13. March 2015
• 1. Referee: Beckmann, Roland
• Signature of the printed copy: 0001/UMC 22806