Characteristics of the internalization signal in the Y543 influenza virus hemagglutinin suggest a model for recognition of internalization signals containing tyrosine.
Several proteins, including the hemagglutinin (HA)-Y543 mutant influenza virus hemagglutinin, are internalized by clathrin-coated pits but do not have a sequence that fits a recently proposed consensus for internalization signals containing tyrosine. To determine whether or not the HA-543 signal is a degenerate form of the internalization signal found in proteins such as the transferrin receptor and mannose 6-phosphate/insulin-like growth factor (IGF) II receptor, we have mutated amino acid positions of HA-Y543 shown to be important for internalization of the two receptors. Our results indicate that the HA-Y543 mutant contains a sub-optimum sequence for a tyrosine-based internalization signal similar to those found in the receptors for transferrin, low density lipoprotein, and mannose 6-phosphate/IGFII. However, amino acids with side chains having very different chemical properties functioned well in positions that are important for the internalization signal. The variety of amino acid side chains found in known internalization sequences suggests that atoms of the polypeptide chain backbone may contribute important interactions for binding proteins to clathrin coats, with many of the side chains serving mainly to permit these interactions, a situation similar to that observed for the binding of peptides by histocompatibility proteins.
Naim
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HY
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Roth
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MG
D000595:Amino Acid Sequence; D002451:Cell Compartmentation; D004705:Endocytosis; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D009980:Influenza A virus / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry
D006389:Hemagglutinins, Viral; D014443:Tyrosine