18-Nov-2021

Julius Rabl (Cryo-EM Knowledge Hub)

16.00 HPM D7.2 and on Zoom external pagehttps://ethz.zoom.us/j/65600733190call_made

Cryo-EM of a large, flexible protein assembly: the GID complex

Abstract
GID is a large E3 ubiquitin ligase involved in human cell cycle regulation. The core complex consists of five subunits and binds additional subunits to recruit substrates with high specificity. In order to understand the structural basis of the observed regulation, we reconstructed in collaboration with Weaam Mohamed (Peter group) a cryo-EM map of the entire GID complex to intermediate resolution. Combination of two cryo-EM maps of different GID complexes with crosslink mass spectrometry data (in collaboration with Alexander Leitner) allowed localizing of the substrate recruitment subunit ARMC8beta. Challenges related to the fragility of the complex, its Megadalton size and high degree of flexibility will be discussed.

(Mohamed WI, Park SL, Rabl J, Leitner A, Boehringer D, Peter M. The human GID complex engages two inde-
pendent modules for substrate recruitment. EMBO Rep. 2021, 22:e52981)