Solution Structure of Tensin2 SH2 Domain and Its Phosphotyrosine-Independent Interaction with DLC-1

Kun Dai,Shanhui Liao,Jiahai Zhang,Xiaoming Tu,Xuecheng Zhang,Dong-Yan Jin

doi:10.1371/journal.pone.0021965

Abstract

BackgroundSrc homology 2 (SH2) domain is a conserved module involved in various biological processes. Tensin family member was reported to be involved in tumor suppression by interacting with DLC-1 (deleted-in-liver-cancer-1) via its SH2 domain. We explore here the important questions that what the structure of tensin2 SH2 domain is, and how it binds to DLC-1, which might reveal a novel binding mode.Principal FindingsTensin2 SH2 domain adopts a conserved SH2 fold that mainly consists of five β-strands flanked by two α-helices. Most SH2 domains recognize phosphorylated ligands specifically. However, tensin2 SH2 domain was identified to interact with nonphosphorylated ligand (DLC-1) as well as phosphorylated ligand.ConclusionsWe determined the solution structure of tensin2 SH2 domain using NMR spectroscopy, and revealed the interactions between tensin2 SH2 domain and its ligands in a phosphotyrosine-independent manner.

Highlights

Src homology 2 (SH2) domain was firstly identified from Nterminal noncatalytic region of fujinami sarcoma virus P130gag-fps
The recombinant protein was expressed in Escherichia coli strain BL21 Gold (DE3) and purified according to previous procedure [23]. 15N-labeled and 13C, 15N-labeled tensin2 SH2 domain were prepared in the same way, except that super broth was replaced by M9 medium containing 0.5 g/L 15N-labeled ammonium chloride and 2.5 g/L 13C-labeled glucose as the sole nitrogen source and carbon source, respectively
The SH2 domains have been found in hundreds of proteins involved in a variety of cellular processes

Summary

Introduction

Src homology 2 (SH2) domain was firstly identified from Nterminal noncatalytic region of fujinami sarcoma virus P130gag-fps. It is a conserved domain of approximately 100 residues and shared by a number of cytoplasmic tyrosine kinase [1]. It is revealed that the C-terminal three residues adjacent to pTyr are critical for the affinity and specificity of SH2 domain-ligand interaction [9,10]. These provide SH2 domain containing proteins with properties of precise recognition of ligands and efficient regulation of signaling pathway. We explore here the important questions that what the structure of tensin SH2 domain is, and how it binds to DLC-1, which might reveal a novel binding mode

Methods

Results

Conclusion