High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3. Academic Article uri icon

Overview

abstract

  • T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) is an important immune regulator. Here, we describe a novel high resolution (1.7 Å) crystal structure of the human (h)TIM-3 N-terminal variable immunoglobulin (IgV) domain with bound calcium (Ca++) that was confirmed by nuclear magnetic resonance (NMR) spectroscopy. Significant conformational differences were observed in the B-C, C'-C″ and C'-D loops of hTIM-3 compared to mouse (m)TIM-3, hTIM-1 and hTIM-4. Further, the conformation of the C-C' loop of hTIM-3 was notably different from hTIM-4. Consistent with the known metal ion-dependent binding of phosphatidylserine (PtdSer) to mTIM-3 and mTIM-4, the NMR spectral analysis and crystal structure of Ca++-bound hTIM-3 revealed that residues in the hTIM-3 F-G loop coordinate binding to Ca++. In addition, we established a novel biochemical assay to define hTIM-3 functionality as determined by binding to human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1). These studies provide new insights useful for understanding and targeting hTIM-3.

publication date

  • November 30, 2018

Research

keywords

  • Crystallography, X-Ray
  • Hepatitis A Virus Cellular Receptor 2
  • Nuclear Magnetic Resonance, Biomolecular
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC6269442

Scopus Document Identifier

  • 85057606166

Digital Object Identifier (DOI)

  • 10.1016/S0969-2126(96)00076-7

PubMed ID

  • 30504845

Additional Document Info

volume

  • 8

issue

  • 1