PChem Seminar – Eric Jacobo

About the event

Speaker: Eric Jacobo

Group: Dr. Jim Brozik

Title: The Sequences Specific Binding and Thermodynamic Driving Forces of the Extended Region of Aquaporin-4 Binding to α-Syntrophin

Abstract

Aquaporin-4 (AQP4) is a water channel protein in the central nervous system (CNS) that supports water homeostasis and neuronal activity. The M23 isoform can form large self-assemblies when unregulated (OAPs). It is especially polarized (concentrated) at the end feet of astrocytes. The extended isoform of AQP4 regulates where OAPs are polarized by binding to the PDZ domain of α-syntrophin, which is part of the dystrophin-associated protein complex (DAPC). The DAPC is associated with the cytoskeleton and the dystroglycans in the extracellular matrix. This complex is vital for cell signaling, and defects in the DAPC contribute to muscular dystrophy. The interactions between the AQP4 extended region and α-syntrophin were unclear until this study. In this talk, we have identified six amino acids critical for AQP4 binding to α-syntrophin. We have measured the dynamics of unbinding and have sequentially replaced each of the six amino acids with alanine to determine which has the greatest effect. We have also measured the thermodynamic driving forces (ΔG, ΔH, and ΔS) of this interaction. In this seminar, we will also present an experimental design for dynamic single-molecule imaging and explain how the data can be used to determine kinetic and thermodynamic parameters.