Exploring absent protein function in yeast: assaying post translational modification and human genetic variation

Authors:

Christina S. Moesslacher1,#, Johanna M. Kohlmayr1,# and Ulrich Stelzl1,#

doi: 10.15698/mic2021.08.756
Volume 8, pp. 164 to 183, published 02/07/2021.

PDF Download PubMed Link
Affiliations:

1 Institute of Pharmaceutical Sciences and BioTechMed-Graz, University of Graz, Graz, Austria.

# Contributed equally to the writing of this review.

Keywords: 

yeast two-hybrid, deep mutational scanning, massively parallel reporter assays, protein-protein interaction, cancer mutations, phosphorylation, DNA methylation.

Corresponding Author(s):

Ulrich Stelzl, University of Graz, Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Universitätsplatz 1/I, A-8010 Graz, Austria, Eu-rope; ulrich.stelzl@uni-graz.at

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Christina S. Moesslacher, Johanna M. Kohlmayr and Ulrich Stelzl (2021). Exploring absent protein function in yeast: assaying post translational modification and human genetic variation. Microbial Cell 8(8): 164-183. doi: 10.15698/mic2021.08.756

© 2021 Moesslacher et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.

Abstract:

Yeast is a valuable eukaryotic model organism that has evolved many processes conserved up to humans, yet many protein functions, including certain DNA and protein modifications, are absent. It is this absence of protein function that is fundamental to approaches using yeast as an in vivo test system to investigate human proteins. Functionality of the heterologous expressed proteins is connected to a quantitative, selectable phenotype, enabling the systematic analyses of mechanisms and specificity of DNA modification, post-translational protein modifications as well as the impact of annotated cancer mutations and coding variation on protein activity and interaction. Through continuous improvements of yeast screening systems, this is increasingly carried out on a global scale using deep mutational scanning approaches. Here we discuss the applicability of yeast systems to investigate absent human protein function with a specific focus on the impact of protein variation on protein-protein interaction modulation.