Reference : Identification of amino acid residues crucial for chemokine receptor dimerization.
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
Identification of amino acid residues crucial for chemokine receptor dimerization.
Hernanz-Falcon, Patricia [> >]
Rodriguez-Frade, Jose Miguel [> >]
Serrano, Antonio [> >]
Juan, David [> >]
del Sol Mesa, Antonio mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Soriano, Silvia F. [> >]
Roncal, Fernando [> >]
Gomez, Lucio [> >]
Valencia, Alfonso [> >]
Martinez-A, Carlos [> >]
Mellado, Mario [> >]
Nature immunology
Yes (verified by ORBilu)
United States
[en] Amino Acids/chemistry ; Animals ; Calcium Signaling/drug effects/immunology ; Cell Line ; Dimerization ; Fluorescence Resonance Energy Transfer ; Humans ; Ligands ; Mice ; Models, Molecular ; Mutagenesis, Site-Directed ; Oligopeptides/chemistry/pharmacology ; Protein Structure, Quaternary ; Receptors, CCR5/chemistry/genetics/metabolism ; Recombinant Proteins/chemistry/genetics/metabolism ; Transfection
[en] Chemokines coordinate leukocyte trafficking by promoting oligomerization and signaling by G protein-coupled receptors; however, it is not known which amino acid residues of the receptors participate in this process. Bioinformatic analysis predicted that Ile52 in transmembrane region-1 (TM1) and Val150 in TM4 of the chemokine receptor CCR5 are key residues in the interaction surface between CCR5 molecules. Mutation of these residues generated nonfunctional receptors that could not dimerize or trigger signaling. In vitro and in vivo studies in human cell lines and primary T cells showed that synthetic peptides containing these residues blocked responses induced by the CCR5 ligand CCL5. Fluorescence resonance energy transfer showed the presence of preformed, ligand-stabilized chemokine receptor oligomers. This is the first description of the residues involved in chemokine receptor dimerization, and indicates a potential target for the modification of chemokine responses.

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