title: An internalization motif is created in the cytoplasmic domain of the transferrin receptor by substitution of a tyrosine at the first position of a predicted tight turn.
abstract: Receptors are internalized from the plasma membrane at approximately 10 times the rate of bulk membrane. The predominant model for the motif that promotes rapid internalization proposes a requirement for a tyrosine located in the first position of a tight turn. In this report we show that an internalization motif can be created de novo by substituting a tyrosine for the first or last residues of a tetrapeptide GDNS (residues 31-34) that is predicted to form a tight turn within the cytoplasmic domain of the human transferrin receptor. These substitutions restore wild-type levels of internalization to transferrin receptors that are poorly internalized due to missense mutations in the native internalization motif. The introduction of a tyrosine at the first or last position of the GDNS tetrapeptide in a transferrin receptor containing an unmodified wild-type internalization motif significantly increases the internalization rate above that of the wild-type receptor. Our results indicate that a functional novel internalization motif can be created by placing specific aromatic amino acids within the overall structure of an existing beta-turn in a cytoplasmic domain of a receptor.
authors.affiliation: Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: B
authors.initials: B
authors.lastname: Pytowski
authors.forename: T W
authors.initials: TW
authors.lastname: Judge
authors.forename: T E
authors.initials: TE
authors.lastname: McGraw
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003593:Cytoplasm / Q000737:chemistry; D004705:Endocytosis; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011990:Receptors, Transferrin / Q000737:chemistry* / Q000378:metabolism; D014443:Tyrosine
chemical_list: D011990:Receptors, Transferrin; D014443:Tyrosine