Evidence for carbohydrate recognition and homotypic and heterotypic binding by the TIM family
Evidence for carbohydrate recognition and homotypic and heterotypic binding by the TIM family
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DOI：
10.1093/intimm/dxm044
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发表时间：
2007-06-01
影响因子：
4.4
通讯作者：
Murphy, Kenneth M.
中科院分区：
文献类型：
--
作者：
Wilker, Peter R.;Sedy, John R.;Murphy, Kenneth M.
T细胞Ig结构域和粘蛋白结构域(TIM)蛋白形成了一个保守的跨膜细胞表面糖蛋白家族，由多种组织表达。每个TIM蛋白含有一个V型Ig结构域、一个糖化粘蛋白样结构域、一个跨膜区和一个细胞质结构域。TIM蛋白识别一系列不同的配体，包括H-铁蛋白、Galectin-9以及其他TIM家族成员。在这项研究中，我们证明了小鼠TIM-1、-3和-4的Ig结构域与小鼠脾细胞和几个非小鼠细胞系表达的配体显示出钙依赖的结合，这表明是非物种特异性的配体识别。此外，各种TIM家族Ig结构域与表面表达的TIM-1和TIM-4的家庭内相互作用需要完整的TIM-1和TIM-4糖基化粘蛋白茎。重要的是，我们还发现了以前未发现的同型TIM相互作用在形成配体-受体对方面的潜力。利用糖链阵列筛选，我们确定了TIM-3Ig结构域识别特定碳水化合物部分的新能力，这表明碳水化合物修饰和蛋白质表位在TIM配体识别中发挥了作用。鉴定TIM蛋白的碳水化合物结合能力有助于解释该家族识别的配体的多样性，并有助于我们理解TIM家族成员之间的同型和异型相互作用。
The T cell Ig domain and mucin domain (TIM) proteins form a conserved family of transmembrane cell-surface glycoproteins expressed by a variety of tissues. Each TIM protein contains a single V-type Ig domain, a glycosylated mucin-like domain, a transmembrane domain and a cytoplasmic domain. TIM proteins recognize a diverse array of ligands, including H-ferritin, galectin-9 as well as other TIM family members. In this study, we demonstrate that the Ig domains of murine TIM-1, -3 and -4 display calcium-dependent binding to ligands expressed by murine splenocytes and several non-murine cell lines, indicating non-species-specific ligand recognition. Further, the intrafamilial interaction of various TIM family Ig domains with surface-expressed TIM-1 and TIM-4 requires an intact TIM-1 and TIM-4 glycosylated mucin stalk. Importantly, we also uncovered the previously unrecognized potential for homotypic TIM interactions in forming ligand-receptor pairs. Using a glycan array screen, we identified the novel capacity of the TIM-3 Ig domain to recognize specific carbohydrate moieties, suggesting a role for carbohydrate modification along with protein epitopes in TIM ligand recognition. Identification of the carbohydrate-binding capacity of TIM proteins helps explain the diversity of ligands recognized by this family and adds to our understanding of homotypic and heterotypic interactions between TIM family members.