title: Alanine substitutions of polar and nonpolar residues in the amino-terminal domain of CCR5 differently impair entry of macrophage- and dualtropic isolates of human immunodeficiency virus type 1.
abstract: Multiple extracellular domains of the CC-chemokine receptor CCR5 are important for its function as a human immunodeficiency virus type 1 (HIV-1) coreceptor. We have recently demonstrated by alanine scanning mutagenesis that the negatively charged residues in the CCR5 amino-terminal domain are essential for gp120 binding and coreceptor function. We have now extended our analysis of this domain to include most polar and nonpolar amino acids. Replacement of alanine with all four tyrosine residues and with serine-17 and cysteine-20 decrease or abolish gp120 binding and CCR5 coreceptor activity. Tyrosine-15 is essential for viral entry irrespective of the test isolate. Substitutions at some of the other positions impair the entry of dualtropic HIV-1 isolates more than that of macrophagetropic ones.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Rabut
authors.forename: J A
authors.initials: JA
authors.lastname: Konner
authors.forename: F
authors.initials: F
authors.lastname: Kajumo
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
authors.forename: T
authors.initials: T
authors.lastname: Dragic
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D010649:Phenylalanine; D000409:Alanine