| Structural highlights
Function
HAVR2_HUMAN Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9.[1] [2]
Publication Abstract from PubMed
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 A) 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.
High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3.,Gandhi AK, Kim WM, Sun ZJ, Huang YH, Bonsor DA, Sundberg EJ, Kondo Y, Wagner G, Kuchroo VK, Petsko G, Blumberg RS Sci Rep. 2018 Nov 30;8(1):17512. doi: 10.1038/s41598-018-35754-0. PMID:30504845[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sanchez-Fueyo A, Tian J, Picarella D, Domenig C, Zheng XX, Sabatos CA, Manlongat N, Bender O, Kamradt T, Kuchroo VK, Gutierrez-Ramos JC, Coyle AJ, Strom TB. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol. 2003 Nov;4(11):1093-101. Epub 2003 Oct 12. PMID:14556005 doi:http://dx.doi.org/10.1038/ni987
- ↑ Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005 Dec;6(12):1245-52. Epub 2005 Nov 13. PMID:16286920 doi:http://dx.doi.org/10.1038/ni1271
- ↑ Gandhi AK, Kim WM, Sun ZJ, Huang YH, Bonsor DA, Sundberg EJ, Kondo Y, Wagner G, Kuchroo VK, Petsko G, Blumberg RS. High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3. Sci Rep. 2018 Nov 30;8(1):17512. doi: 10.1038/s41598-018-35754-0. PMID:30504845 doi:http://dx.doi.org/10.1038/s41598-018-35754-0
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