6DHB

Crystal structure of the human TIM-3 with bound Calcium

Summary for 6DHB

• Entry DOI: 10.2210/pdb6dhb/pdb
• Descriptor: Hepatitis A virus cellular receptor 2, CALCIUM ION, BENZOIC ACID, ... (5 entities in total)
• Functional Keywords: t cell immunoglobulin mucin-3 immunological tolerance, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 12499.34

Authors

Gandhi, A.K.,Kim, W.M.,Huang, Y.H.,Bonsor, D.,Sundberg, E.,Sun, Z.-Y.,Petsko, G.A.,Kuchroo, V.,Blumberg, R.S. (deposition date: 2018-05-19, release date: 2018-12-12, Last modification date: 2024-10-30)

Primary citation

Gandhi, A.K.,Kim, W.M.,Sun, Z.J.,Huang, Y.H.,Bonsor, D.A.,Sundberg, E.J.,Kondo, Y.,Wagner, G.,Kuchroo, V.K.,Petsko, G.,Blumberg, R.S.
High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3.
Sci Rep, 8:17512-17512, 2018

PubMed 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.

PubMed: 30504845
DOI: 10.1038/s41598-018-35754-0

Experimental method

X-RAY DIFFRACTION (1.7 Å)