Effect of Toxic Metal Binding on Tax-Interacting Protein1 (TIP1): A Protein Related to Brain Diseases

Abstract

Human tax-interacting protein1 (TIP1), also known as glutaminase-interacting protein (GIP), is a small globular protein containing a PDZ domain. PDZ domains are the most common protein-protein interaction modules present in eukaryotes. In humans, TIP1 plays a very important role in many cellular pathways including β-catenin-mediated Wnt signaling, Rho-activator rhotekin-mediated Rho signaling pathway, and glutamate signaling pathway for the normal activity of the central nervous system. TIP1 also regulates potassium channel expression in the plasma membrane and is a binding partner to many proteins including viral oncoproteins, HTLV-1 Tax and HPV16 E6. Since TIP1 is at a pivotal point in many cellular processes through its interaction with a growing list of partner proteins, any impact on the proper functioning of this protein can have severe consequences on the well-being of a living system. Although metals are essential for plants and animals in trace amounts, elevated levels of heavy metals such as arsenic, cadmium, zinc, and lead are toxic causing various health problems including cardiovascular disorders, neuronal damage, renal injuries, and cancer. Here, we report the effect of heavy metals, arsenic and cadmium, on TIP1 conformation using circular dichroism and fluorescence spectroscopy techniques. Our study revealed these metals have a significant impact on the structure of TIP1 even at very low levels.