T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface Journal Article
| Authors: | Cao, E.; Zang, X.; Ramagopal, U. A.; Mukhopadhaya, A.; Fedorov, A.; Fedorov, E.; Zencheck, W. D.; Lary, J. W.; Cole, J. L.; Deng, H.; Xiao, H.; DiLorenzo, T. P.; Allison, J. P.; Nathenson, S. G.; Almo, S. C. |
| Article Title: | T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface |
| Abstract: | The T cell immunoglobulin mucin (Tim) family of receptors regulates effector CD4+ T cell functions and is implicated in autoimmune and allergic diseases. Tim-3 induces immunological tolerance, and engagement of the Tim-3 immunoglobulin variable (IgV) domain by galectin-9 is important for appropriate termination of T helper 1-immune responses. The 2 Å crystal structure of the Tim-3 IgV domain demonstrated that four cysteines, which are invariant within the Tim family, form two noncanonical disulfide bonds, resulting in a surface not present in other immunoglobulin superfamily members. Biochemical and biophysical studies demonstrated that this unique structural feature mediates a previously unidentified galectin-9-independent binding process and suggested that this structural feature is conserved within the entire Tim family. The current work provided a graphic example of the relationship between sequence, structure, and function and suggested that the interplay between multiple Tim-3-binding activities contributes to the regulated assembly of signaling complexes required for effective Th1-mediated immunity. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; mutant protein; protein conformation; protein domain; protein analysis; mouse; animals; mice; cells, cultured; signaling; protein; protein binding; wild type; receptors, virus; cellular immunity; amino acid sequence; molecular sequence data; ligands; crystal structure; crystallography, x-ray; protein structure, tertiary; th1 cell; protein structure; protein family; structure analysis; galectin; molimmuno; ligand binding; cysteine; humdisease; ecalectin; protein tim 3; galectins |
| Journal Title: | Immunity |
| Volume: | 26 |
| Issue: | 3 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2007-03-23 |
| Start Page: | 311 |
| End Page: | 321 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2007.01.016 |
| PUBMED: | 17363302 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 32" - "Export Date: 17 November 2011" - "CODEN: IUNIE" - "Source: Scopus" |
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