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

Biology

Smita Mohanty¹  Mohiuddin Ovee²  Monimoy Banerjee¹ 

[1] Department of Chemistry, Oklahoma State University, Stillwater, OK 74078, USA;

关键词: PDZ;    TIP-1;    GIP;    NMR;    structure;    function;    peptide motif;   

DOI  :  10.3390/biology4010088

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.