scholarly journals Receptor-binding domain of murine leukemia virus envelope glycoproteins.

1995 ◽  
Vol 69 (2) ◽  
pp. 713-719 ◽  
Author(s):  
J L Battini ◽  
O Danos ◽  
J M Heard
Keyword(s):  
Receptor Binding ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Binding Domain ◽  
Envelope Glycoproteins ◽  
Receptor Binding Domain ◽  
Virus Envelope ◽  
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.

scholarly journals Envelope Proteins Containing Single Amino Acid Substitutions Support a Structural Model of the Receptor-Binding Domain of Bovine Leukemia Virus Surface Protein

2002 ◽  
Vol 76 (21) ◽  
pp. 10861-10872 ◽  
Author(s):  
Elizabeth R. Johnston ◽  
Lorraine M. Albritton ◽  
Kathryn Radke
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Bovine Leukemia Virus ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Binding Domain ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Env Protein ◽  
Murine Leukemia

ABSTRACT Functional domains of the strikingly conserved envelope (Env) glycoproteins of bovine leukemia virus (BLV) and its close relative, human T-cell leukemia virus type 1 (HTLV-1), are still being defined. We have used BLV Env protein variants to gain insights into the structure and function of this important determinant of viral infectivity. Each of 23 different single amino acid variants found in cDNA clones of env transcripts present after short-term culture of peripheral blood mononuclear cells from BLV-infected sheep was expressed in COS-1 cells and tested for the ability to mediate cell fusion and to be cleaved to surface (SU) and transmembrane (TM) protein subunits. Of 11 Env variants that failed to induce syncytia or did so poorly, 7 contained changes in amino acids identical or chemically conserved in the HTLV-1 Env protein. These seven included the four variants that showed aberrant proteolytic cleavage and poor cell surface expression, underscoring their importance for Env structure. Ten of 12 variants that retained wild-type syncytium-inducing ability clustered in the N-terminal half of BLV SU, which forms the putative receptor-binding domain (RBD). Several variants in the RBD showed evidence of subtle misfolding, as judged by reduced binding to monoclonal antibodies recognizing conformational epitopes F, G, and H formed by the N terminus of SU. We modeled the BLV RBD by aligning putative structural elements with known elements of the ecotropic Friend murine leukemia virus RBD monomer. All the variant RBD residues but one are exposed on the surface of this BLV model. These variants as well as function-altering, antibody-reactive residues defined by other investigators group on one face of the molecular model. They are strikingly absent from the opposite face, implying that it is likely to face inward in Env complexes. This surface might interact with the C-terminal domain of SU or with an adjacent monomer in the Env oligomer. This location suggests an orientation for the monomer of ecotropic Friend murine leukemia virus RBD.

Role of N-linked Glycosylation in the Activity of the Friend Murine Leukemia Virus SU Protein Receptor-Binding Domain

Virology ◽  
1994 ◽  
Vol 202 (1) ◽  
pp. 496-499 ◽  
Author(s):  
Jean-Luc Battini ◽  
Samuel C. Kayman ◽  
Abraham Pinter ◽  
Jean Michel Heard ◽  
Olivier Danos
Keyword(s):  
Receptor Binding ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Protein Receptor ◽  
Murine Leukemia

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.

Characterization of R peptide of murine leukemia virus envelope glycoproteins in syncytium formation and entry

2007 ◽  
Vol 152 (12) ◽  
pp. 2169-2182 ◽  
Author(s):  
Y. Kubo ◽  
C. Tominaga ◽  
H. Yoshii ◽  
H. Kamiyama ◽  
C. Mitani ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Syncytium Formation ◽  
Envelope Glycoproteins ◽  
Virus Envelope ◽  
Murine Leukemia

scholarly journals Activation of Membrane Fusion by Murine Leukemia Viruses Is Controlled in cis or in trans by Interactions between the Receptor-Binding Domain and a Conserved Disulfide Loop of the Carboxy Terminus of the Surface Glycoprotein

2001 ◽  
Vol 75 (8) ◽  
pp. 3685-3695 ◽  
Author(s):  
Dimitri Lavillette ◽  
Bertrand Boson ◽  
Stephen J. Russell ◽  
François-Loı̈c Cosset
Keyword(s):  
Membrane Fusion ◽  
Receptor Binding ◽  
Leukemia Virus ◽  
Binding Domain ◽  
Surface Glycoprotein ◽  
Receptor Binding Domain ◽  
Domain Interactions ◽  
Carboxy Terminal ◽  
Leukemia Viruses ◽  
Murine Leukemia

ABSTRACT Cell entry of retroviruses is initiated by the recognition of cellular receptors and the subsequent membrane fusion between viral and cellular membranes. These two steps are mediated by the surface (SU) and transmembrane (TM) subunits of the retroviral envelope glycoprotein (Env), respectively. Determinants regulating membrane fusion have been described throughout SU and TM, but the processes coupling receptor recognition to fusion are still elusive. Here we establish that a critical interaction is formed between the receptor-binding domain (RBD) and the major disulfide loop of the carboxy-terminal domain (C domain) of the murine leukemia virus SU. Receptor binding causes an alteration of this interaction and, in turn, promotes further events of Env fusion activation. We characterize mutations which, by lowering this interaction and reducing the compatibility between the RBD and C domains of Env glycoprotein chimeras, affect both Env fusogenicity and sensitivity to receptor interference. Additionally, we demonstrate that suboptimal interactions in such mutant Env proteins can be compensated in trans by soluble RBDs in a manner that depends on their compatibility with the C domain. Our results therefore indicate that RBD/C domain interactions may occur in cis, via the proper RBD of the viral Env itself, or in trans, via a distinct RBD expressed by virion-free Env glycoproteins expressed endogenously by the infected cells or provided by neighboring Env trimers.

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