A single amino acid deletion at the amino terminus of influenza virus hemagglutinin causes malfolding and blocks exocytosis of the molecule in mammalian cells.
I am investigating the role of protein folding in the transport of influenza virus hemagglutinin (HA), a membrane-bound protein, along the exocytotic pathway. From a previous work (Gething, M.-J., McCammon, K., and Sambrook, J. (1986) Cell 46, 939-950), it has been shown that a subset of alterations of the COOH-terminal sequences of the HA molecule inhibit folding and impede its transport to the cell surface. Current studies establish that the integrity of the NH2-terminal sequences of the HA is essential for assembly and transport of the molecule. Mutants lacking just 1 or 2 amino acids immediately COOH-terminal to the signal cleavage site are translocated and core glycosylated, but also incorrectly folded. The mutant molecules are not terminally glycosylated and are thus confined inside the cells. A hypothesis will be presented to explain why sequences at opposite ends of the HA molecule are essential for the assembly of native structures and why correct folding is necessary for transport along the exocytotic pathway of mammalian cells.
Chao
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Department of Biochemistry, Chang Gung Medical College, Taoyuan, Taiwan, Republic of China.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D004247:DNA / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005089:Exocytosis; D005455:Fluorescent Antibody Technique; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics* / Q000378:metabolism; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008322:Mammals; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011487:Protein Conformation
D000596:Amino Acids; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D004247:DNA