Especially in higher eukaryotes, during and following translation, proteins can be modified in highly diverse ways. A very frequently occurring protein modification is the acetylation of a protein’s amino-terminus (N-terminus). While this modification changes the biophysical parameters of the protein’s N-terminus, surprisingly little is known about the functional consequences, if any, of this modification for the grand majority of affected proteins. Recent studies indicated the possibility that an N-terminal acetyl group can affect protein folding and thus protein conformation.
In this project we will improve a mass spectrometry-based method for assessing protein conformation on a cellular scale. This method will then be applied to the proteomes of human cell lines that are models for human diseases. Selected proteins with altered conformation will be further validated using other molecular technologies by which we hope to get more insights in protein folding diseases, amongst others.
Our aim is thus to evaluate the absence or reduction of N-terminal acetylation on a proteome’s conformation.