The role of electrostatic interactions in SH3 domain structure and function. (360G-Wellcome-211881_Z_18_Z)

Cell signalling involves protein-protein interactions. The most common module for binding is the SH3 domains, over 400 of which are encoded for in humans. Electrostatics play a key role between negative binding surfaces and positive peptides, but it isn’t fully known how conserved this is amongst family members. We will investigate the conservation of electrostatic binding amongst the yeast SH3 domain family and orthologs of the Abp1 SH3 domain. This will involve using domains and domain-peptide hybrids with several biophysical techniques to give us the necessary thermodynamic measurements to analyse the strength of binding and stability. We will vary NaCl buffer concentrations to investigate the stability of domains and the strength of the interaction with domain-peptide hybrids. It is hypothesized that at higher NaCl concentrations, domain stability will be stronger, however the peptide interaction will be weaker. We expect salt will affect the family members differently but overall electrostatic interactions will be conserved as an essential feature. A deeper understanding of electrostatics in peptide interactions will help us to develop peptide inhibitors to block cancerous signalling pathways and therefore be developed as therapeutics for treatment against cancers.