scholarly journals Identification of a Receptor-Binding Pocket on the Envelope Protein of Friend Murine Leukemia Virus

1999 ◽  
Vol 73 (5) ◽  
pp. 3758-3763 ◽  
Author(s):  
Robert A. Davey ◽  
Yi Zuo ◽  
James M. Cunningham
Keyword(s):  
Receptor Binding ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Binding Pocket ◽  
Fusion Pore ◽  
Detectable Effect ◽  
Virus Envelope ◽  
Receptor Binding Site ◽  
Murine Leukemia

ABSTRACT Based on previous structural and functional studies, a potential receptor-binding site composed of residues that form a pocket at one end of the two long antiparallel helices in the receptor-binding domain of Friend 57 murine leukemia virus envelope protein (RBD) has been proposed. To test this hypothesis, directed substitutions for residues in the pocket were introduced and consequences for infection and for receptor binding were measured. Receptor binding was measured initially by a sensitive assay based on coexpression of receptor and RBD inXenopus oocytes, and the findings were confirmed by using purified proteins. Three residues that are critical for both binding and infection (S84, D86, and W102), with side chains that extend into the pocket, were identified. Moreover, when mCAT-1 was overexpressed, the infectivity of Fr57-MLV carrying pocket substitutions was partially restored. Substitutions for 18 adjacent residues and 11 other previously unexamined surface-exposed residues outside of the RBD pocket had no detectable effect on function. Taken together, these findings support a model in which the RBD pocket interacts directly with mCAT-1 (likely residues, Y235 and E237) and multiple receptor-envelope complexes are required to form the fusion pore.

scholarly journals Immunoprotective Determinants in Friend Murine Leukemia Virus Envelope Protein

Virology ◽  
1998 ◽  
Vol 248 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Kim J. Hasenkrug ◽  
Diane M. Brooks ◽  
Michael N. Robertson ◽  
R.V. Srinivas ◽  
Bruce Chesebro
Keyword(s):  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Virus Envelope ◽  
Virus Envelope Protein ◽  
Murine Leukemia

scholarly journals A Hydrophobic Patch in Ecotropic Murine Leukemia Virus Envelope Protein Is the Putative Binding Site for a Critical Tyrosine Residue on the Cellular Receptor

1999 ◽  
Vol 73 (12) ◽  
pp. 10164-10172 ◽  
Author(s):  
Tatiana Zavorotinskaya ◽  
Lorraine M. Albritton
Keyword(s):  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Wild Type Virus ◽  
Wild Type ◽  
Virus Binding ◽  
Virus Envelope ◽  
Virus Envelope Protein ◽  
Putative Binding Site ◽  
Murine Leukemia

ABSTRACT In the receptor for ecotropic murine leukemia viruses, tyrosine 235 contributes a critical hydrophobic side chain to the virus-receptor interaction (14). Here we report that tryptophan 142 in ecotropic Moloney murine leukemia virus envelope protein is essential to virus binding and infection. Replacement of tryptophan 142 by alanine or serine resulted in misfolding. However, replacement by methionine (W142M) allowed correct folding of the majority of glycoprotein molecules. W142M virus showed a marked reduction in virus binding and was almost noninfectious, suggesting that tryptophan 142 is involved in receptor binding. In contrast, W142Y virus containing a replacement of tryptophan 142 with an aromatic residue (tyrosine) was as efficient as wild-type virus in infection and binding of cells expressing the wild-type receptor. However, W142Y virus was 100-fold less efficient than wild-type virus in infection of cells expressing a mutant receptor containing tryptophan instead of the critical tyrosine. These results strongly support tryptophan 142 being an essential residue on the virus envelope protein that interacts directly with the critical hydrophobic residue at position 235 of the ecotropic receptor. Tryptophan 142 forms one side of a shallow hydrophobic pocket on the surface of the envelope protein, suggesting that it might comprise the complete putative binding site for tyrosine 235. We discuss the implications of our findings with respect to two models of the envelope protein trimer. Interestingly, both models place tryptophan 142 at the interface between adjacent subunits of the trimer.

scholarly journals Murine Leukemia Virus Envelope Protein in Transgenic-Mouse Serum Blocks Infection In Vitro

1998 ◽  
Vol 72 (10) ◽  
pp. 8462-8462 ◽  
Author(s):  
Abdallah Nihrane ◽  
Kazunobu Fujita ◽  
Ron Willey ◽  
Myung Soo Lyu ◽  
Jonathan Silver
Keyword(s):  
Transgenic Mouse ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Mouse Serum ◽  
Virus Envelope ◽  
Virus Envelope Protein ◽  
Murine Leukemia

scholarly journals Role of Variable Regions A and B in Receptor Binding Domain of Amphotropic Murine Leukemia Virus Envelope Protein

1998 ◽  
Vol 72 (11) ◽  
pp. 9101-9108 ◽  
Author(s):  
Jin-Young Han ◽  
Yi Zhao ◽  
W. French Anderson ◽  
Paula M. Cannon
Keyword(s):  
Receptor Binding ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Variable Regions ◽  
Amino Terminal ◽  
Amphotropic Murine Leukemia Virus ◽  
Murine Leukemia

ABSTRACT For the amphotropic murine leukemia virus (MuLV), a 208-amino-acid amino-terminal fragment of the surface unit (SU) of the envelope glycoprotein is sufficient to bind to its receptor, Pit2. Within this binding domain, two hypervariable regions, VRA and VRB, have been proposed to be important for receptor recognition. In order to specifically locate residues that are important for the interaction with Pit2, we generated a number of site-specific mutations in both VRA and VRB and analyzed the resulting envelope proteins when expressed on retroviral vectors. Concurrently, we substituted portions of the amphotropic SU with homologous regions from the polytropic MuLV envelope protein. The amphotropic SU was unaffected by most of the point mutations we introduced. In addition, the deletion of eight residues in a region of VRA that was previously suggested to be essential for Pit2 utilization only decreased titer on NIH 3T3 cells by 1 order of magnitude. Although the replacement of the amino-terminal two-thirds of VRA with the polytropic sequence abolished receptor binding, smaller nonoverlapping substitutions did not affect the function of the protein. We were not able to identify a single critical receptor contact point within VRA, and we suggest that the amphotropic receptor binding domain probably makes multiple contacts with the receptor and that the loss of some of these contacts can be tolerated.

Sign in / Sign up

Export Citation Format

Share Document