Functional classification of immune regulatory proteins.
Functional classification of immune regulatory proteins.
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DOI:
10.1016/j.str.2013.02.022
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发表时间:
2013-05-07
期刊:
影响因子:
5.7
通讯作者:
Fiser, Andras
中科院分区:
文献类型:
--
作者:
Rubinstein, Rotem;Ramagopal, Udupi A.;Nathenson, Stanley G.;Almo, Steven C.;Fiser, Andras
Summary The members of the immunoglobulin superfamily (IgSF) control innate and adaptive immunity, and are prime targets for the treatment of autoimmune diseases, infectious diseases and malignancies. We describe a computational method, termed the Brotherhood Algorithm, which utilizes intermediate sequence information to classify proteins into functionally related families. This approach identifies previously unrecognized functional relationships within the IgSF and predicts the existence of new receptor-ligand interactions. As a specific example, we describe new members of the nectin/nectin-like family of cell adhesion and signaling proteins, as well as new receptor-ligand interactions within this family. Guided by the Brotherhood approach, we present the high resolution structural characterization of a previously undescribed homophilic interaction involving the class-I MHC-restricted T-cell-associated molecule (CRTAM) – a newly defined nectin-like family member. The Brotherhood Algorithm is likely to have significant impact on structural immunology by identifying those proteins and complexes for which structural characterization will be particularly informative.
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