Exploring the molecular insights of intrinsically disordered mitochondrial intermembrane protein in its unbound and substrate-bound state

Abstract

ABSTRACT Intrinsically disordered proteins (IDPs) are a major class of proteins that remain biologically active despite lacking a proper tertiary structure. They can adopt a fold when bound with the substrate. Mitochondrial Intermembrane space import and assembly protein 40 (Mia40) come under the category of membrane IDP. This protein plays a vital role in the import, oxidation, and folding of other mitochondrial proteins. Cox17 being an important substrate of Mia40 is also an IDP that induces conformational changes in Mia40 upon binding. In this study, we focused on analysing the effects of the intrinsically disordered regions (IDR’s) in Mia40 and the presence of Cox17 in inducing conformational changes in Mia40. The conformational changes in the lipid environment were analysed using the molecular dynamics studies in the presence and absence of IDR’s and Cox17. Cox17 and Mia40 IDR’s influence in the water transport mechanism across the membrane were analysed using water dynamics. The results show that the Cox17 binding has induced the formation of an α-helical structure in the IDR residues of Mia40. Both the IDR residues and Cox17 enhance the water pore formation through the mitochondrial membrane.