Cryo-EM analysis of the active post-translational Sec translocon

Weng, Tsai-Hsuan (2021): Cryo-EM analysis of the active post-translational Sec translocon. Dissertation, LMU München: Fakultät für Chemie und Pharmazie

Abstract

In eukaryotes, most secretory and membrane proteins are targeted by an N-terminal signal sequence to the endoplasmic reticulum, where the heterotrimeric Sec61 complex serves as protein-conducting channel. In the post-translational mode, fully synthesized proteins are recognized by a specialized channel, called the Sec complex, consisting of the Sec61 complex and additional Sec62, Sec63, Sec71 and Sec72 subunits. Recent structures of this Sec complex in the idle state revealed the overall architecture in a pre-opened state. In this thesis, a cryo-EM structure of the Sec complex bound to a substrate is presented. The signal sequence was inserted into the lateral gate of Sec61α similar to previous structures, yet, with the gate adopting an even more open conformation. The signal sequence was flanked by two Sec62 transmembrane helices, the cytoplasmic N-terminal domain of Sec62 was more rigidly positioned, and the plug domain was relocated. Together, a near complete and integrated model of the active Sec complex was achieved.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: post-translational translocation, protein translocation, sec complex, signal sequence, Sec62
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 540 Chemie
• Fakultäten: Fakultät für Chemie und Pharmazie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 28. April 2021
• 1. Bericht­erstatter:in: Beckmann, Roland