PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins

Abstract

Cellular signaling is primarily directed via protein-protein interactions. PDZ (PSD-95/Discs large/ZO-1 homologous) domains are well known protein-protein interaction modules involved in various key signaling pathways. Human Tax-interacting protein 1 (TIP-1), also known as glutaminase interaction protein (GIP), is a Class I PDZ domain protein that recognizes the consensus binding motif X-S/T-X-V/I/L-COOH of the C-terminus of its target proteins. We recently reported that TIP-1 not only interacts via the C-terminus of its target partner proteins but also recognizes an internal motif defined by the consensus sequence S/T-X-V/L-D in the target protein. Identification of new target partners containing either a C-terminal or internal recognition motif has rapidly expanded the TIP-1 protein interaction network. TIP-1 being composed solely of a single PDZ domain is unique among PDZ containing proteins. Since it is involved in many important signaling pathways, it is a possible target for drug design. In this mini review, we have discussed human TIP-1, its structure, mechanism of function, its interactions with target proteins containing different recognition motifs, and its involvement in human diseases. Understanding the molecular mechanisms of TIP-1 interactions with distinct target partners and their role in human diseases will be useful for designing novel therapeutics.

Recent advances in shear‐thinning and self‐healing hydrogels for biomedical applications

“…PDZ domains are ~90 residues in size and adopt a common fold consisting of β‐barrel capped by α‐helices . Human tax‐interacting protein (TIP‐1) consists of a single PDZ domain, encompassing residues 13–112 of the 124‐amino acid protein . TIP‐1 and its ligand have been used to construct a two‐component self‐assembling hydrogel, where the interaction can be reinforced via disulfide linkages .…”

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

“…[33][34][35] Human TIP1 is involved in various signaling pathways controlling key biological processes including regulation of the cerebral concentration of neurotransmitter glutamate, β-catenin-mediated Wnt signaling, Rho-activator Rhotekin, and potassium channel Kir2.3 signaling pathway. 11,16,[24][25][26]36 Considering the importance of TIP1 for the well-being of a living cell, it is of great importance to investigate the effect of toxic metals on the structure of TIP1 and consequently on its function below levels that are currently allowed. We report here the effects of two metals, arsenic and cadmium, on TIP1 structure/conformation.…”

“…33-35 Human TIP1 is involved in various signaling pathways controlling key biological processes including regulation of the cerebral concentration of neurotransmitter glutamate, β-catenin-mediated Wnt signaling, Rho-activator Rhotekin, and potassium channel Kir2.3 signaling pathway. 11,16,24-26,36…”

Crispr Knockout of Tax1bp3 Reduces Expression of P53 in Human Papilloma Negative and Human Papilloma Positive Cervical Carcinoma Cells.

“…Introduction:-Tax1BP3(Tax 1binding protein 3), also known as Tax interacting protein 1 (Tip-1) or glutaminase interacting protein (GIP) is a multifunctional protein targeting many proteins in diverse signaling pathways involved in cancer and other disease (Mohanty et al, 2015). Tax1BP3 consists of single PDZ domain which makes Tax1BP3 unique since other PDZ proteins possess multiple PDZ domains (Wang et al, 2014).…”