A Novel Protease Processing Site in the Transframe Protein of Human T-Cell Leukemia Virus Type 1 PR76gag-pro Defines the N Terminus of RT

A Novel Protease Processing Site in the Transframe Protein of Human T-Cell Leukemia Virus Type 1 PR76gag-pro Defines the N Terminus of RT
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人 T 细胞白血病病毒 1 型 PR76gag-pro 转架蛋白中的新型蛋白酶加工位点定义了 RT 的 N 末端

DOI:
10.1128/jvi.76.24.13101-13105.2002
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发表时间:
2002
影响因子:
5.4
通讯作者:
D. Derse
D. Derse
中科院分区:
医学2区
文献类型:
--
作者:
G. Heidecker;S. Hill;P. Lloyd;D. Derse

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人t细胞白血病病毒1型的基因组RNA编码Gag、Gag- pro和Gag- pro - pol三种多蛋白,它们分别在没有、一次和两次帧移的情况下被翻译。在这篇报告中,我们证明在Gag-Pro前体的C端编码的77个残基可以在病毒粒子中共同检测到一个8 kda的转框蛋白(TFP)。具有c端截断TFP(19,32或50个残基)的突变病毒在体外基本上具有野生型表型。然而,由于第二个移码位点的突变,仅编码Gag和Gag- pro - pol多蛋白的病毒突变体不产生TFP,因此是非传染性的。对PR和TFP之间的蛋白水解裂解位点进行突变分析,发现存在一个额外的位点,并且存在一个p1肽将蛋白酶和TFP分离。虽然去除PR-p1连接的切割位点对病毒复制有一定的影响,但p1-TFP切割位点的突变导致非传染性病毒和逆转录酶活性的丧失。对血凝素标记RT的氨基末端序列的测定表明,Gag- pro - pol前体的加工使用了相同的位点,从而定义了成熟RT的开始。无论是单独突变还是组合突变都不会改变Gag多蛋白的数量或加工模式,这表明蛋白酶的活性独立于其C端。
ABSTRACT The genomic RNA of human T-cell leukemia virus type 1 encodes three polyproteins, Gag, Gag-Pro, and Gag-Pro-Pol, which are translated as a result of no, one, and two frameshifts, respectively. In this report we demonstrate that the 77 residues encoded at the C terminus of the Gag-Pro precursor can be collectively detected as an 8-kDa transframe protein (TFP) in virions. Mutant viruses with a C-terminally truncated TFP (19, 32, or 50 residues) had essentially a wild-type phenotype in vitro. However, a virus mutant that encoded only the Gag and Gag-Pro-Pol polyproteins due to a mutation in the second frameshift site, and hence did not produce TFP, was noninfectious. Mutation analysis of the proteolytic cleavage site between PR and TFP revealed the presence of an additional site and the existence of a p1 peptide separating protease and TFP. While removal of the cleavage site at the PR-p1 junction had a modest effect on virus replication, mutation of the p1-TFP cleavage site led to noninfectious virus and the loss of reverse transcriptase activity. Determination of the amino-terminal sequence of a hemagglutinin-tagged RT demonstrated that the same site is used in processing the Gag-Pro-Pol precursor and thus defines the start of mature RT. Neither mutation alone or in combination caused changes in the amounts or processing patterns of the Gag polyprotein, indicating that protease is active independent of its C terminus.
卡波西肉瘤细胞中炎症反应基因的抗氧化敏感调节。
DOI: 10.1097/00042560-199609000-00001
发表时间: 1996
期刊: Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association
影响因子: --
作者:
Offermann,MK;Lin,JC;Mar,EC;Shaw,R;Yang,J;Medford,RM
通讯作者: Medford,RM
人 T 细胞嗜淋巴细胞病毒 1 逆转录酶的蛋白水解加工:通过质谱法鉴定 N 末端切割位点。
DOI: 10.1006/abbi.2001.2432
发表时间: 2001
期刊: Archives of biochemistry and biophysics.
影响因子: --
作者:
Agbuya,PG;Sherman,NE;Moen,LK
通讯作者: Moen,LK