Functional classification of immune regulatory proteins

Rotem Rubinstein, Udupi A. Ramagopal, Stanley G. Nathenson, Steven C. Almo, Andras Fiser

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 functional relationships within the IgSF and predicts additional receptor-ligand interactions. As a specific example, we examine the nectin/nectin-like family of cell adhesion and signaling proteins and propose receptor-ligand interactions within this family. Guided by the Brotherhood approach, we present the high-resolution structural characterization of a homophilic interaction involving the class-I MHC-restricted T-cell-associated molecule, which we now classify as a nectin-like family member. The Brotherhood algorithm is likely to have a significant impact on structural immunology by identifying those proteins and complexes for which structural characterization will be particularly informative.

Original languageEnglish (US)
Pages (from-to)766-776
Number of pages11
Issue number5
StatePublished - May 7 2013

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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