Functional clustering of immunoglobulin superfamily proteins with protein-protein interaction information calibrated hidden Markov model sequence profiles.
Functional clustering of immunoglobulin superfamily proteins with protein-protein interaction information calibrated hidden Markov model sequence profiles.
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DOI：
10.1016/j.jmb.2013.11.009
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发表时间：
2014-02-20
影响因子：
5.6
通讯作者：
Fiser, Andras
中科院分区：
文献类型：
--
作者：
Yap, Eng-Hui;Rosche, Tyler;Almo, Steve;Fiser, Andras
免疫球蛋白超家族（IgSF）的分泌和细胞表面定位成员在调节适应性和先天性免疫应答中起核心作用，并且是开发基于蛋白质的治疗剂的主要靶标。这些蛋白质的胞外域的基本活性是同源配体的特异性识别，所述同源配体通常是IgSF的其他成员。在这项工作中，我们提供了这类重要的蛋白质的功能的洞察力，通过开发一个聚类算法，组在一起的IgSF细胞外结构域具有类似的结合偏好。从隐马尔可夫模型为基础的序列概况和结构域的信息进行校准对人工策划的蛋白质相互作用数据，以定义IgSF蛋白的功能家族。该方法能够将477个细胞外IgSF蛋白中的82%分配到功能家族，而其余的是具有独特功能的单一蛋白质或无法用当前技术分配的蛋白质。IgSF蛋白的功能聚类产生关于鉴定新的同源受体：配体对的假设，并将可能的相互作用伴侣的库减少到可管理的水平以进行实验验证。
Secreted and cell surface-localized members of the immunoglobulin superfamily (IgSF) play central roles in regulating adaptive and innate immune responses, and are prime targets for the development of protein-based therapeutics. An essential activity of the ectodomains of these proteins is the specific recognition of cognate ligands, which are often other members of the IgSF. In this work we provide functional insight for this important class of proteins through the development of a clustering algorithm that groups together extracellular domains of the IgSF with similar binding preferences. Information from hidden Markov model-based sequence profiles and domain structure is calibrated against manually curated protein interaction data to define functional families of IgSF proteins. The method is able to assign 82% of the 477 extracellular IgSF protein to a functional family, while the rest are either single proteins with unique function or proteins that could not be assigned with the current technology. The functional clustering of IgSF proteins generates hypotheses regarding the identification of new cognate receptor:ligand pairs and reduces the pool of possible interacting partners to a manageable level for experimental validation.
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