Structural and functional characterization of the E3 ligase BIRC6

Bc. Sascha GRATZL

Master's thesis

Regulation and structural organization of higher-order protein complexes implicated in prokaryotic and eukaryotic stress response

Abstract:

The aim of the thesis was to characterize the ubiquitin ligase BIRC6 in several contexts. The goal was to expand the knowledge on the selectivity of E1-E2 recognition, to increase the known substrate range of BIRC6, and to elucidate the molecular interactions fulfilled by BIRC6 during autophagy via interaction with GABARAP. In addition, it was aimed to gain a better understanding on the general ubiquitination mechanism in E2/E3 hybrid enzymes, to identify the ubiquitination sites of known apoptotic and autophagic substrates and to enlighten substrate recognition by BIRC6.

Abstract:

The aim of the thesis was to characterize the ubiquitin ligase BIRC6 in several contexts. The goal was to expand the knowledge on the selectivity of E1-E2 recognition, to increase the known substrate range of BIRC6, and to elucidate the molecular interactions fulfilled by BIRC6 during autophagy via interaction with GABARAP. In addition, it was aimed to gain a better understanding on the general ubiquitination mechanism in E2/E3 hybrid enzymes, to identify the ubiquitination sites of known apoptotic and autophagic substrates and to enlighten substrate recognition by BIRC6.

Keywords

structural biology, cryo-EM, x-ray crystallography, autophagy, apoptosis, inhibitor of apoptosis proteins, AlphaFold2, ATG8, ubiquitin, E3 ligase

Language used: English

Date on which the thesis was submitted / produced: 15. 12. 2023

Thesis defence

• Supervisor: RNDr. Ján Štěrba, Ph.D., Tim Clausen

UNIVERSITY OF SOUTH BOHEMIA IN ČESKÉ BUDĚJOVICE

Faculty of Science

Master programme / field:
Biological Chemistry / Biological Chemistry