Associate Professor Andrew Brown's laboratory investigates the complex repetoire of signals that help to balance cholesterol levels in our cells.
Role of Post-translational Modifications in the Protein-Protein Interaction Network
We have built global protein interaction networks using the GEOMI software. This has shown us that proteins participate in a stunning number and variety of interactions inside a cell. What is the role of post-translational modifications here?
It is known that certain interactions can only occur when particular amino acids carry certain modifications. For example, a protein carrying an SH2 domain will only be able to interact with another protein that has a particular phosphorylated (but not unphosphorylated) tyrosine residue. However, the extent to which this molecular switch is used to control the assembly and disassembly of protein complexes - and thus control protein function - is not known.
It is our hypothesis that modification-dependent interactions serve as a fundamental method for controlling protein complexes and protein function, but this needs to be proven. This project will use proteome-wide screens for reversible post-translational modifications such as methylation and acetylation, and map these on to the protein interaction network. We will consider where the modified amino acids are found, and the domains present in any interaction partners. We may examine mutant strains or cell lines to better understand this.
Reference:
- Wilkins MR, Kummerfeld SK (2008) Sticking together? Falling apart? Exploring the dynamics of the interactome. Trends in Biochemical Sciences, 33: 195-200.
BABS personnel that are responsible for this project