title: Functional classification of immune regulatory proteins.
abstract: 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.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Rotem
authors.initials: R
authors.lastname: Rubinstein
authors.forename: Udupi A
authors.initials: UA
authors.lastname: Ramagopal
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Nathenson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
authors.forename: Andras
authors.initials: A
authors.lastname: Fiser
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002448:Cell Adhesion; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data
chemical_list: D007136:Immunoglobulins; D008024:Ligands