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Project

Are amino-terminal proteoforms engaged in different protein complexes?

Cells produce an unexpected high number of protein variants that start at sites that differ from the anticipated start site. Most of these amino(N)-terminal variants or proteoforms are shorter than the expected protein, though some carry N-terminal extensions when ribosomes start translating from sites present in the annotated 5’ untranslated regions of transcripts. Close to one-fifth of all identified protein N-termini in higher eukaryotes point to the existence of such N-terminal proteoforms, thus leading to even more complex proteomes than anticipated, and a major question emerging now is on the functional impact of these N-terminal proteoforms. We previously demonstrated that N-terminal protein variants made from the same gene may have different stabilities in cells. We now hypothesize that N-terminal proteoforms might end up in different, yet unexplored protein complexes. To assess this, we will start by constructing a comprehensive catalogue of N-terminal proteoforms expressed by a human cell line. Secondly, bioinformatics will be used to select up to 100 human genes that encode different N-terminal proteoforms. Third, a novel technology for assessing protein-protein interactions, Virotrap, will be used and further developed for characterizing the interactomes of these proteoforms. Finally, selected interactions will be validated in appropriate models and the functions of N-terminal proteoforms will be investigated at the cellular level.

Date:1 Jan 2018 →  31 Dec 2021
Keywords:N-terminus, proteoforms, protein-protein interactions
Disciplines:Molecular and cell biology not elsewhere classified