The basolateral targeting signal in the cytoplasmic domain of glycoprotein G from vesicular stomatitis virus resembles a variety of intracellular targeting motifs related by primary sequence but having diverse targeting activities.
Using systematic site-directed mutagenesis, the basolateral targeting signal in the cytoplasmic domain of glycoprotein G from vesicular stomatitis virus (VSV G) has been localized to an 11-amino acid sequence, which contains two essential residues and a third that makes a minor contribution. A tyrosine at position 19 of the 29-residue carboxyl-terminal cytoplasmic tail is the most important residue and cannot be replaced by other aromatic amino acids, while an isoleucine at position 22, 3 residues carboxyl-terminal to this tyrosine, is also critical but can be replaced by other aliphatic residues. Additionally, an arginine at position 16 makes a minor contribution. Therefore the crucial elements of this targeting signal can be represented by the sequence Y-X-X-aliphatic. While earlier investigation has suggested similarity between basolateral targeting and internalization signals, alignment of this sequence with other cytoplasmic targeting signals suggests the existence of a broad class of homologous targeting motifs that direct protein delivery to a variety of cellular locations. This in turn suggests the existence of a family of homologous receptors, distributed throughout the cell, which differ in their affinity for subsets of these targeting sequences.
Thomas
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DC
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Roth
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MG
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D004705:Endocytosis; D005814:Genes, Viral; D007668:Kidney; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017354:Point Mutation; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins