Advanced electron paramagnetic resonance (EPR) techniques combined with computational approaches to study protein compelexes of ankyrin.
The ankyrins are a family of ubiquitous structural proteins which coordinate numerous integral membrane proteins involved in ion transport, cell adhesion, or membrane trafficking into specific nano- or mcrodomains and couple them to the spectrin-actin cytoskeleton. These microdomains have a critical role in controlling and coordinating the electrogenic and signal transduction properties of cell membranes, while the coupling of integral membrane proteins to the cytoskeleton plays a critical role in maintaining the stability and other mechanical properties of cell membranes. In erythrocytes, ankyrinR binds to the cytoplasmic domain of the membrane protein band 3 (CDB3). The shape, deformability, and durability of erythrocytes all depend critically on this interaction. Naturally occurring genetic mutations that cause defects in this interaction result in hereditary spherocytosis characterized by abnormally shaped and fragile red blood cells.
The overall goal of this work is to understand the extraordinary protein architecture created by ankyrin-R and band 3 with an emphasis on the polyvalent interactions involving the membrane binding domain of ankyrin-R.