Abstract
Coxsackie and adenovirus receptor (CAR) is the primary cellular receptor for group B coxsackieviruses and most adenovirus serotypes and plays a crucial role in adenoviral gene therapy. Recent discovery of the interaction between junctional adhesion molecule-like protein (JAML) and CAR uncovered important functional roles in immunity, inflammation, and tissue homeostasis. Crystal structures of JAML ectodomain (2.2 angstroms) and its complex with CAR (2.8 angstroms) reveal an unusual immunoglobulin-domain assembly for JAML and a charged interface that confers high specificity. Biochemical and mutagenesis studies illustrate how CAR-mediated clustering of JAML recruits phosphoinositide 3-kinase (P13K) to a JAML intracellular sequence motif as delineated for the alphabeta T cell costimulatory receptor CD28. Thus, CAR and JAML are cell signaling receptors of the immune system with implications for asthma, cancer, and chronic nonhealing wounds.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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CD28 Antigens / metabolism
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CHO Cells
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Cell Adhesion Molecules / chemistry*
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Cell Adhesion Molecules / metabolism*
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Chemical Phenomena
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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Cricetinae
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Cricetulus
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Crystallization
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Crystallography, X-Ray
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Epithelium / immunology
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Glycosylation
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Ligands
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Mice
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Phosphatidylinositol 3-Kinases / metabolism*
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Protein Interaction Domains and Motifs
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Protein Multimerization
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Protein Structure, Tertiary
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Receptors, Antigen, T-Cell, gamma-delta / immunology
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Receptors, Antigen, T-Cell, gamma-delta / metabolism
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Receptors, Virus / chemistry*
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Receptors, Virus / metabolism*
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Signal Transduction*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
Substances
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CD28 Antigens
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CLMP protein, mouse
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Cell Adhesion Molecules
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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Ligands
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Virus
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Phosphatidylinositol 3-Kinases