Analysis of the murine ecotropic leukemia virus receptor reveals a common biochemical determinant on diverse cell surface receptors that is essential to retrovirus entry

Sonal Malhotra, Amy G. Scott, Tatiana Zavorotinskaya, Lorraine Albritton

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Two residues, tyrosine 235 and glutamic acid 237, of the ecotropic marine leukemia virus receptor (ATRC1) have been shown to be essential for receptor-mediated virus envelope binding and entry. We performed genetic analyses to examine the biochemical contribution of these residues in a productive virus-receptor interaction. Altered ATRC1 receptors bearing either a phenylalanine, a tryptophan, a histidine, or a methionine at position 235 mediated ecotropic virus entry comparable to that mediated by ATRC1. In contrast, altered ATRC1 receptors bearing alanine, threonine, serine, or proline at position 235 exhibited a 300- to 10,000-fold decrease in receptor capability. Furthermore, substitution of tyrosine or phenylalanine into the corresponding position (242) of the homologous human protein that lacks ecotropic virus receptor capability resulted in acquisition of ecotropic virus receptor function comparable to that of ATRC1. Substitution of a tryptophan or a histidine at that position of the human protein, however, resulted in a much-reduced receptor capability, suggesting a preference for a benzene ring in the hydrophobic side chain. A similar analysis of proteins substituted at position 237 revealed that aspartic acid, but not arginine or lysine, can functionally substitute for glutamic acid 237 in ATRC1 or at the corresponding position in the human protein. These results suggest a requirement for an acidic and a nearby hydrophobic amino acid for efficient ecotropic virus entry. Similar motifs have been identified in the virus binding sites of other retrovirus receptors, suggesting that the initial step of retrovirus entry may be governed by a common mechanism.

Original languageEnglish (US)
Pages (from-to)321-326
Number of pages6
JournalJournal of Virology
Volume70
Issue number1
StatePublished - 1996

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Cationic Amino Acid Transporter 1
Retroviridae
Murine leukemia virus
Cell Surface Receptors
Virus Receptors
Virus Internalization
receptors
Virus Attachment
viruses
cells
Phenylalanine
glutamic acid
histidine
Histidine
phenylalanine
Tryptophan
tryptophan
Tyrosine
tyrosine
Glutamic Acid

All Science Journal Classification (ASJC) codes

  • Immunology

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Analysis of the murine ecotropic leukemia virus receptor reveals a common biochemical determinant on diverse cell surface receptors that is essential to retrovirus entry. / Malhotra, Sonal; Scott, Amy G.; Zavorotinskaya, Tatiana; Albritton, Lorraine.

In: Journal of Virology, Vol. 70, No. 1, 1996, p. 321-326.

Research output: Contribution to journalArticle

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