Role of variable regions A and B in receptor binding domain of amphotropic murine leukemia virus envelope protein

被引:29
作者
Han, JY
Zhao, Y
Anderson, WF
Cannon, PM
机构
[1] Univ So Calif, Sch Med, Norris Canc Ctr, Gene Therapy Labs, Los Angeles, CA 90033 USA
[2] Univ So Calif, Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
关键词
D O I
10.1128/JVI.72.11.9101-9108.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 rc:cognition. 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 carl be tolerated.
引用
收藏
页码:9101 / 9108
页数:8
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