Identification of an extracellular domain within the human PiT2 receptor that is required for amphotropic murine leukemia virus binding
Identification of an extracellular domain within the human PiT2 receptor that is required for amphotropic murine leukemia virus binding
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DOI：
10.1128/jvi.78.2.595-602.2004
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发表时间：
2004-01-01
影响因子：
5.4
通讯作者：
Eiden, MV
中科院分区：
文献类型：
--
作者：
Feldman, SA;Farrell, KB;Eiden, MV
人PiT 2（PiT 2）是一种多跨膜蛋白，作为III型磷酸钠协同转运蛋白和嗜酸性鼠白血病病毒（A-MuLV）的受体发挥作用。人PiT 1（PiT 1），另一种III型磷酸钠协同转运蛋白，是一种高度相关的蛋白质，作为巨猿白血病病毒的受体发挥作用，但不作为A-MuLV的受体。PiT 1和PiT 2作为具有独特性质的离散病毒受体发挥作用的能力大概反映在这两种蛋白质之间的关键残基差异中。早期绘制PiT 2内对病毒结合和/或进入重要的区域的努力依赖于用在中国仓鼠卵巢（CHOK 1）细胞中表达的PiT 1-PiT 2嵌合cDNA获得的感染结果。这些定位PiT 2病毒结合位点的尝试受到阻碍，因为它们是基于感染性而不是结合测定，因此，结合但未能促进病毒进入的受体无法与不结合病毒的受体区分开来。使用更准确的拓扑模型PiT 2以及A-MuLV受体结合试验，我们已经确定了人PiT 2受体的细胞外结构域1（ECD 1）对于A-MuLV结合和感染是重要的。
Human PiT2 (PiT2) is a multiple-membrane-spanning protein that functions as a type III sodium phosphate cotransporter and as the receptor for amphotropic murine leukemia virus (A-MuLV). Human PiT1 (PiT1), another type III sodium phosphate cotransporter, is a highly related protein that functions as a receptor for gibbon ape leukemia virus but not for A-MuLV. The ability of PiT1 and PiT2 to function as discrete viral receptors with unique properties presumably is reflected in critical residue differences between these two proteins. Early efforts to map the region(s) within PiT2 that is important for virus binding and/or entry relied on infection results obtained with PiT1-PiT2 chimeric cDNAs expressed in Chinese hamster ovary (CHOK1) cells. These attempts to localize the PiT2 virus-binding site were hampered because they were based on infectivity, not binding, assays, and therefore, receptors that bound but failed to facilitate virus entry could not be distinguished from receptors that did not bind virus. Using a more accurate topological model for PiT2 as well as an A-MuLV receptor-binding assay, we have identified extracellular domain one (ECD1) of the human PiT2 receptor as being important for A-MuLV binding and infection.