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

SUBMITTER: Gandhi AK 

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

REPOSITORIES: biostudies-literature