| First Author | Cao E | Year | 2007 |
| Journal | Immunity | Volume | 26 |
| Issue | 3 | Pages | 311-21 |
| PubMed ID | 17363302 | Mgi Jnum | J:120159 |
| Mgi Id | MGI:3703963 | Doi | 10.1016/j.immuni.2007.01.016 |
| Citation | Cao E, et al. (2007) T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface. Immunity 26(3):311-21 |
| abstractText | 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 A 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. |
