Effect of pH on the structure and stability of irisin, a multifunctional protein: Multispectroscopic and molecular dynamics simulation approach

Abstract

Irisin is a potential therapeutic agent to prevent or treat various metabolic-related disorders and neurodegenerative diseases viz. Alzheimer’s disease (AD). In this study, we have employed a multispectroscopic approach to elucidate the structural and conformational changes in the irisin at varying pH (pH 2.0 to 12.0). The spectroscopic measurements revealed that irisin maintains its structure (both secondary and tertiary) in the alkaline pH range, with minimal structural changes observed across it. However, secondary and tertiary structural alterations were evident across the acidic pH range. CD spectroscopy suggested a gain of the secondary structure in the acidic pH range, implying that irisin is more stable at acidic pH, with maximum stability and compactness observed at pH 4.0. In vitro observations were further validated by in silico studies. Molecular dynamics simulation also suggested that irisin assumes higher stability in the conformational space at pH 4.0 and 6.0 than the rest of the system. This study can serve as a platform to delineate the enhanced functionality of irisin at lower pH that can be implicated in developing therapies for metabolic disorders, including diabetes and obesity