Title :

Elucidating the Structural Basis of Substrate Recognition by the Proteasomes: A Global Approach

Abstract :

PSMD9, a non-ATPase subunit of the 19S regulatory complex of the 26S proteasome harbours an uncharacterized PDZ-like domain which is well known for protein-protein interaction. PDZ domains interact with C-terminal residues of the interacting partner. In quest for partners of PSMD9, we performed C-terminal tetrapeptide screen representing the C-termini of proteins of human proteome to test the ability of these peptides to bind to PSMD9 and consequently demonstrate that proteins harbouring those C-terminal residues interact with PSMD9. Here, we report that PSMD9 interacts with the C-terminal residues of hnRNPA1, S14, a ligand growth hormone and IL6 receptor via its PDZ-like domain. Studies in our lab have also shown that PSMD9-hnRNPA1 interaction is important for NF-κB signaling. Through homology modeling, docking studies, site directed mutagenesis and simulation, we provide an insight into the probable structure of PDZ domain of PSMD9 and the residues important for the interaction and functions of PSMD9.