IISER MOHALI

Abstract:
Intrinsically disordered proteins (IDPs) lack stable secondary and tertiary structure under physiological conditions in the absence of their biological partners and thus exist as dynamic ensembles of interconverting conformers, often highly soluble in water. However, in some cases, IDPs such as the ones involved in neurodegenerative diseases can form protein aggregates and their aggregation process may be triggered by the interaction with membranes. While the interfacial behaviour of globular proteins has been extensively studied, experimental data on IDPs at the air/water (A/W) and water/lipid interfaces are scarce. I will present here the interfacial properties of the intrinsically disordered C-terminal domain of the Hendra virus nucleoprotein (N TAIL ) studied by tensiometry using Langmuir films and an automated drop tensiometer and by interfacial spectroscopy using polarization modulated-infrared reflection–absorption spectroscopy (PM-IRRAS) and compared them to those of lysozyme taken as a model globular protein of similar molecular mass. Although it is depleted in hydrophobic/aromatic residues, N TAIL shows a significant surfaceactivity, with a higher adsorption capacity at the A/W interface and penetration into egg phosphatidylcholine monolayer compared to lysozyme. While lysozyme remains folded uponcompression of the protein layer at the A/W interface and shows a quasi-pure elastic behaviour, N TAIL shows a much higher molecular area and forms a highly viscoelastic film with a high dilational modulus. While N TAIL is known to form a helix upon interaction with its protein partner within the Hendra virus replication machinery, it shows a different disorder-to-order transition and folds into an anti-parallel beta-sheet at the A/W interface and presents strong intermolecular interactions. I will complete this presentation with an overview of protein disorder in proteins/enzymes interacting with lipid droplets.