2OYP

T Cell Immunoglobulin Mucin-3 Crystal Structure Revealed a Galectin-9-independent Binding Surface

Summary for 2OYP

• Entry DOI: 10.2210/pdb2oyp/pdb
• Descriptor: Hepatitis A virus cellular receptor 2, SULFATE ION (3 entities in total)
• Functional Keywords: tim-3; t-cell immunoglobulin mucin, signaling protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 12514.41

Authors

Cao, E.,Ramagopal, U.A.,Fedorov, A.A.,Fedorov, E.V.,Nathenson, S.G.,Almo, S.C. (deposition date: 2007-02-22, release date: 2007-04-10, Last modification date: 2024-10-30)

Primary citation

Cao, E.,Zang, X.,Ramagopal, U.A.,Mukhopadhaya, A.,Fedorov, A.A.,Fedorov, E.V.,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.
T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface
Immunity, 26:311-321, 2007

PubMed 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 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.

PubMed: 17363302
DOI: 10.1016/j.immuni.2007.01.016

Experimental method

X-RAY DIFFRACTION (1.952 Å)