Santiago César, Ballesteros Angela, Martínez-Muñoz Laura, Mellado Mario, Kaplan Gerardo G, Freeman Gordon J, Casasnovas José M
Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain.
Immunity. 2007 Dec;27(6):941-51. doi: 10.1016/j.immuni.2007.11.008.
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.
T细胞免疫球蛋白和粘蛋白结构域（TIM）蛋白是T细胞应答的重要调节因子。小鼠TIM-4的晶体结构在TIM家族的免疫球蛋白（Ig）结构域中确定了一个金属离子依赖性配体结合位点（MILIBS）。TIM结构域的特征性CC'环和疏水性FG环形成了一个狭窄的腔，酸性化合物可穿透该腔并与结合在TIM蛋白保守残基上的金属离子配位。与Ig结构域结合的磷脂酰丝氨酸的结构表明，亲水头部穿透进入MILIBS并与金属离子配位，而FG环末端的芳香族残基与脂肪酸链相互作用并可插入脂质双层。我们的结果还揭示了MILIBS在TIM-1转运至细胞表面过程中的重要作用。
