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Title: Functional Classification of Immune Regulatory Proteins

Abstract

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. We were guided by the Brotherhood approach and 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:
 [1];  [1];  [1];  [1];  [1]
  1. Albert Einstein College of Medicine, Bronx, NY (United States)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1229091
Report Number(s):
BNL-111166-2015-JA
Journal ID: ISSN 0969-2126
DOE Contract Number:
SC00112704
Resource Type:
Journal Article
Resource Relation:
Journal Name: Structure; Journal Volume: 21; Journal Issue: 5
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Rubinstein, Rotem, Ramagopal, Udupi A., Nathenson, Stanley G., Almo, Steven C., and Fiser, Andras. Functional Classification of Immune Regulatory Proteins. United States: N. p., 2013. Web. doi:10.1016/j.str.2013.02.022.
Rubinstein, Rotem, Ramagopal, Udupi A., Nathenson, Stanley G., Almo, Steven C., & Fiser, Andras. Functional Classification of Immune Regulatory Proteins. United States. doi:10.1016/j.str.2013.02.022.
Rubinstein, Rotem, Ramagopal, Udupi A., Nathenson, Stanley G., Almo, Steven C., and Fiser, Andras. Wed . "Functional Classification of Immune Regulatory Proteins". United States. doi:10.1016/j.str.2013.02.022.
@article{osti_1229091,
title = {Functional Classification of Immune Regulatory Proteins},
author = {Rubinstein, Rotem and Ramagopal, Udupi A. and Nathenson, Stanley G. and Almo, Steven C. and Fiser, Andras},
abstractNote = {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. We were guided by the Brotherhood approach and 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.},
doi = {10.1016/j.str.2013.02.022},
journal = {Structure},
number = 5,
volume = 21,
place = {United States},
year = {Wed May 01 00:00:00 EDT 2013},
month = {Wed May 01 00:00:00 EDT 2013}
}
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