Intermolecular Cystine-Bonding of Murine Interleukin 2 Indicates that Ligand Dimerization is Important for the Formation of the High-Affinity Receptor Complex
作者:
LotherHeinz,
MütherHorst,
GessnerAndré,
AbdallahSaid,
KüklhlckeKlaus,
期刊:
Growth Factors
(Taylor Available online 1992)
卷期:
Volume 7,
issue 2
页码: 117-129
ISSN:0897-7194
年代: 1992
DOI:10.3109/08977199209046401
出版商: Taylor&Francis
关键词: interleukin 2;homodimers;cystine-bonding;amphiphilicαhelix;binding;internalization
数据来源: Taylor
摘要:
AbstractInterleukin 2 is thought to be active as a monomeric protein. As the nonessential Cys-140 of murine interleukin 2 (mIL2) is located in the hydrophobic interface of the amphiphilic F domain it was successfully used to stabilize hydrophobic amino acid contacts between two mIL2 cores yielding biologically active cystine-bonded dimeric mIL2. (3H) thymidine incorporation assays with intermolecular cystine-bonded or monomeric mIL2 revealed almost identical median effective concentrations (EC50) and high-affinity dissociation constants (Kdh), respectively. Comparative binding and internalization assays suggest that one cystine-bonded dimeric or two monomeric mIL2 molecules bind to the high-affinity receptor complex. Furthermore, DSS concentration-dependent crosslinking studies using monomeric mIL2 revealed four membrane-derived protein-complexes with apparent molecular weights of about 70 kDa, 85 kDa, 95 kDa and 100 kDa, respectively, showing that both mIL2 receptor chains may be crosslinked to a monomeric or dimeric ligand molecule, respectively. We therefore propose that dimerization of murine interleukin 2 occurring either in solution at concentrations above the low-affinity dissociation constant or at the low-affinity receptor is important for regulation of high-affinity complex formation and signal transduction.
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