Dataset Information

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

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.

SUBMITTER: Gandhi AK

PROVIDER: S-EPMC6269442 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gandhi Amit K AK Kim Walter M WM Sun Zhen-Yu J ZJ Huang Yu-Hwa YH Bonsor Daniel A DA Sundberg Eric J EJ Kondo Yasuyuki Y Wagner Gerhard G Kuchroo Vijay K VK Petsko Gregory G Blumberg Richard S RS

Scientific reports 20181130 1

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<sup>++</sup>) 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, th ...[more]

PMID: 30504845

Similar Datasets

Project description:Background and aims T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is mainly expressed by immune cells and plays an immunomodulatory role in cardiovascular disease. However, the prognostic value of Tim-3 in acute decompensated heart failure (ADHF) is unclear. This study aimed to investigate the expression profile of Tim-3 on CD4+ and CD8+ T cells in patients with ADHF and its impact on their prognosis. Methods In this prospective study, 84 patients who were hospitalized with ADHF and 83 patients without heart failure were enrolled. Main clinical data were collected during patient visits. The Tim-3 expression on CD4+ and CD8+ T cells in peripheral blood samples was assayed by flow cytometry. Long-term prognosis of the patients with ADHF was evaluated by major adverse cardiac and cerebrovascular events (MACCE) over a 12-month follow-up period. Results We found that the Tim-3 expression on CD4+ T cells [2.08% (1.15–2.67%) vs. 0.88% (0.56–1.39%), p < 0.001] and CD8+ T cells [3.81% (2.24–6.03%) vs. 1.36% (0.76–3.00%), p < 0.001] in ADHF group were significantly increased vs. the non-ADHF group. Logistic analysis revealed that high levels of Tim-3 expressed on CD4+ and CD8+ T cells were independent risk factors of ADHF (OR: 2.76; 95% CI: 1.34–5.65, p = 0.006; OR: 2.58; 95% CI: 1.26–5.31, p = 0.010, respectively). ROC curve analysis showed that the high level of Tim-3 on CD4+ or CD8+ T cells as a biomarker has predictive performance for ADHF (AUC: 0.75; 95% CI: 0.68–0.83; AUC: 0.78, 95% CI: 0.71–0.85, respectively). During a median follow-up of 12 months, the Cox regression analysis revealed that higher Tim-3 on CD4+ and CD8+ T cells were strongly associated with increased risks of MACCE within 12 months after ADHF (HR: 2.613; 95% CI: 1.11–6.13, p = 0.027; HR: 2.762, 95% CI: 1.15–6.63, p = 0.023; respectively). Conclusion Our research indicated that the expression level of Tim-3 on CD4+ and CD8+ T cells, elevated in patients with ADHF, was an independent predictor of MACCE within 12 months after ADHF. It suggests a potential immunoregulatory role of Tim-3 signaling system in the mechanism of ADHF.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets