Scientists Image Atomic Structure of Critical Protein

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Researchers found new insights of human T-cell immunoglobulin and mucin domain containing protein-3 (hTIM-3) by studying its atomic structure at Brigham and Women’s Hospital.

Human T-cell immunoglobulin and mucin domain containing protein-3 (hTIM-3) is a protein that in humans is encoded by the HAVCR2 gene. A new study conducted at Brigham and Women’s Hospital by investigators samples the atomic structure of hTIM-3 protein. This might provide new insights for targeting this protein for numerous cancer and autoimmune therapeutics, which is currently under clinical development. The findings of this study were published online in Scientific Reports on Nov. 30.

Richard Blumberg, MD, chief of the Division of Gastroenterology, Hepatology and Endoscopy in the Department of Medicine and senior author of the study, said: “The hTIM-3 protein is an important immune regulator, yet it has been difficult to target for drug development as high-resolution structure conformational details have been elusive. We resolved the structure of hTIM-3 and established a novel biochemical assay to define its functionality, which will be useful for understanding the role of hTIM-3 in the immune system.”

Using the location of calcium atoms, which serves as an essential co-factor that binds to the hTIM-3 IgV domain, the team captured a high-resolution X-ray crystal structure and nuclear magnetic resonance (NMR) image of the hTIM-3 IgV domain.

Amit Gandhi, Ph.D., a researcher in Blumberg’s laboratory in the Department of Medicine and author of the study, said: “This is the first NMR analysis of any immune-related TIM molecule and the first high resolution structural report of the hTIM-3 IgV domain with association of critical co-factors such as calcium.”

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Cynthia Carrier is a graduate of Texas A&M, where she played volleyball and annoyed a lot of professors. Now as Plains Gazette's entertainment and Lifestyle Editor, she enjoys writing about delicious BBQ, outrageous style trends and all things Texas.