Structures of T Cell Immunoglobulin Mucin Protein 4 Show a Metal-Ion-Dependent Ligand Binding Site where Phosphatidylserine Binds

The T cell immunoglobulin and mucin domain (TIM) proteins are important regulators of T cell responses. Crystal structures of the murine TIM-4 identified a metal-ion-dependent ligand binding site (MILIBS) in the immunoglobulin (Ig) domain of the TIM family. The characteristic CC′ loop of the TIM dom...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2007-12, Vol.27 (6), p.941-951
Main Authors: Santiago, César, Ballesteros, Angela, Martínez-Muñoz, Laura, Mellado, Mario, Kaplan, Gerardo G., Freeman, Gordon J., Casasnovas, José M.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Asthma
Autoimmune diseases
Binding Sites
Cell Line
Crystal structure
Crystallization
Data processing
Humans
Immunoglobulin Variable Region - chemistry
Ligands
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Metals - chemistry
Molecular Sequence Data
MOLIMMUNO
Phosphatidylserines - metabolism
Protein Transport
Proteins
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Summary:The T cell immunoglobulin and mucin domain (TIM) proteins are important regulators of T cell responses. Crystal structures of the murine TIM-4 identified a metal-ion-dependent ligand binding site (MILIBS) in the immunoglobulin (Ig) domain of the TIM family. The characteristic CC′ loop of the TIM domain and the hydrophobic FG loop shaped a narrow cavity where acidic compounds penetrate and coordinate to a metal ion bound to conserved residues in the TIM proteins. The structure of phosphatidylserine bound to the Ig domain showed that the hydrophilic head penetrates into the MILIBS and coordinates with the metal ion, whereas the aromatic residues on the tip of the FG loop interacted with the fatty acid chains and could insert into the lipid bilayer. Our results also revealed an important role of the MILIBS in the trafficking of TIM-1 to the cell surface.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2007.11.008