TY - JOUR
T1 - Structural basis for binding multiple ligands by the common cytokine receptor γ-chain
AU - Olosz, Ferenc
AU - Malek, Thomas R.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/4/5
Y1 - 2002/4/5
N2 - The common γ-chain (γc) that functions both in ligand binding and signal transduction is a shared subunit of the multichain receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The structural basis by which the ectodomain of γc contributes to binding six distinct cytokines is only partially defined. In the present study, epitope mapping of antagonistic anti-γc monoclonal antibodies led to the identification of Asn-128 of mouse γc that represents another potential contact residue that is required for binding IL-2, IL-7, and IL-15 but not IL-4. In addition, Tyr-103, Cys-161, Cys-210, and Cys-211, previously identified to contribute to binding IL-2 and IL-7, were also found to be involved in binding IL-4 and IL-15. Collectively, these data favor a model in which γc utilizes a common mechanism for its interactions with multiple cytokines, and the binding sites are largely overlapping but not identical. Asn-128 and Tyr-103 likely act as contact residues whereas Cys-161, Cys-210, and Gly211 may stabilize the structure of the proposed ligand-interacting surface formed by the two extracytoplasmic domains.
AB - The common γ-chain (γc) that functions both in ligand binding and signal transduction is a shared subunit of the multichain receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The structural basis by which the ectodomain of γc contributes to binding six distinct cytokines is only partially defined. In the present study, epitope mapping of antagonistic anti-γc monoclonal antibodies led to the identification of Asn-128 of mouse γc that represents another potential contact residue that is required for binding IL-2, IL-7, and IL-15 but not IL-4. In addition, Tyr-103, Cys-161, Cys-210, and Cys-211, previously identified to contribute to binding IL-2 and IL-7, were also found to be involved in binding IL-4 and IL-15. Collectively, these data favor a model in which γc utilizes a common mechanism for its interactions with multiple cytokines, and the binding sites are largely overlapping but not identical. Asn-128 and Tyr-103 likely act as contact residues whereas Cys-161, Cys-210, and Gly211 may stabilize the structure of the proposed ligand-interacting surface formed by the two extracytoplasmic domains.
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U2 - 10.1074/jbc.M110520200
DO - 10.1074/jbc.M110520200
M3 - Article
C2 - 11815609
AN - SCOPUS:0037023689
VL - 277
SP - 12047
EP - 12052
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 14
ER -