The birth of protein complexes

Project Information

ComplexAssembly

Grant agreement ID: 724349

DOI

10.3030/724349

Project closed

EC signature date 3 February 2017

Start date 1 February 2018

End date 31 January 2023

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 957 717,00

EU contribution

€ 1 957 717,00

Coordinated by

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Periodic Reporting for period 4 - ComplexAssembly (The birth of protein complexes)

Reporting period: 2022-07-01 to 2023-01-31

Summary of the context and overall objectives of the project

Proteins constitute the individual building blocks of life on the molecular level. They are often gathered into physically associated groups of multiple proteins, so-called protein complexes that form the major functional units inside of living cells. Faithful protein complex assembly is fundamentally important for cellular homeostasis but little is known about the very transient molecular events that occur during the early steps of this process. This project aims to understand the order in which protein complexes are assembled, to investigate if this physical association already occurs during protein synthesis and to visualize the transient intermediates of assembly. The knowledge generated during this project will be of high relevance for scenarios under which a cell’s protein quality control system has to cope with stress, such as aging and neurodegenerative diseases. It might also facilitate the more efficient industrial production of therapeutically relevant proteins.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We have worked on method development for the identification of proteins that associate with each other already during synthesis and for the visualization of protein complex assembly intermediates. We applied these methods to the nuclear pore complex, one of the most intricate protein complexes. We have, at least in part, determined the order in which the individual proteins that constitute these complexes are assembled. We identified a subset of components that is synthesized directly at the sites of biogenesis, implying physical association during synthesis. We furthermore found that importins may bind to nascent cargos already at the exit tunnel of the ribosome.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We found that the order of assembly is context-dependent. In this particular case, it differs during oogenesis and early embryogenesis as compared to somatic cells. We focus our efforts on the more precise elucidation of the early steps of assembly and the visualization of intermediates. We furthermore found a chaperoning role of importins during protein complex formation.