An alpha-helical signal in the cytosolic domain of the interleukin 2 receptor beta chain mediates sorting towards degradation after endocytosis.
High-affinity IL2 receptors consist of three components, the alpha, beta, and gamma chains that are associated in a noncovalent manner. Both the beta and gamma chains belong to the cytokine receptor superfamily. Interleukin 2 (IL2) binds to high-affinity receptors on the cell surface and IL2-receptor complexes are internalized. After endocytosis, the components of this multimolecular receptor have different intracellular fates: one of the chains, alpha, recycles to the plasma membrane, while the others, beta and gamma, are routed towards late endocytic compartments and are degraded. We show here that the cytosolic domain of the beta chain contains a 10-amino acid sequence which codes for a sorting signal. When transferred to a normally recycling receptor, this sequence diverts it from recycling. The structure of a 17-amino acid segment of the beta chain including this sequence has been studied by nuclear magnetic resonance and circular dichroism spectroscopy, which revealed that the 10 amino acids corresponding to the sorting signal form an amphipathic alpha helix. This work thus describes a novel, highly structured signal, which is sufficient for sorting towards degradation compartments after endocytosis.
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Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, Paris, France.
Delepierre
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Dautry-Varsat
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D000595:Amino Acid Sequence; D000596:Amino Acids; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D003600:Cytosol; D004705:Endocytosis / Q000502:physiology*; D006367:HeLa Cells; D019077:Helix-Turn-Helix Motifs; D006801:Humans; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D002966:Clathrin; D015375:Receptors, Interleukin-2; D014168:Transferrin