Cytomegalovirus assembly protein precursor and proteinase precursor contain two nuclear localization signals that mediate their own nuclear translocation and that of the major capsid protein.
Cytomegalovirus assembly protein precursor and proteinase precursor contain two nuclear localization signals that mediate their own nuclear translocation and that of the major capsid protein.
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巨细胞病毒组装蛋白前体和蛋白酶前体含有两个核定位信号，介导其自身的核易位和主要衣壳蛋白的核易位。
DOI：
10.1128/jvi.72.10.7722-7732.1998
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发表时间：
1998
影响因子：
5.4
通讯作者：
Gibson,W
中科院分区：
文献类型：
--
作者：
Plafker,SM;Gibson,W
巨细胞病毒（CMV）组装蛋白前体（pAP）与主要衣壳蛋白（MCP）相互作用，这种相互作用是MCP核易位所必需的，否则MCP仍留在转染细胞的细胞质中（L. J. Wood等，J. Virol. 71:179-190, 1997）。我们对这一发现进行了解释，表明CMV MCP缺乏自身的核定位信号（NLS），并利用pAP作为携带NLS的护卫进入细胞核。巨细胞病毒pAP氨基酸序列有两个基本残基（例如，猴巨细胞病毒的KRRRER [NLS1]和KARKRLK [NLS2]）与猴病毒40大t抗原NLS相似（D. Kalderon et al., Cell 39:49 - 509, 1984），其中一个（NLS1）在其他疱疹病毒的pAP同源物中有对应。本研究表明NLS1和NLS2是相互独立的NLS，它们可以(i)将pAP和相关蛋白酶前体（pNP1）切口转运到细胞核中，（ii）转运MCP到细胞核中。通过使用NLS突变体和羧基末端缺失结构的组合，我们证明了pAP的自相互作用以及pAP与pNP1和pNP1与自身的细胞质相互作用。这些发现与衣壳组装的早期步骤，MCP核运输的机制以及可能的原衣壳亚结构的细胞质形成的相关性进行了讨论。
The cytomegalovirus (CMV) assembly protein precursor (pAP) interacts with the major capsid protein (MCP), and this interaction is required for nuclear translocation of the MCP, which otherwise remains in the cytoplasm of transfected cells (L. J. Wood et al., J. Virol. 71:179–190, 1997). We have interpreted this finding to indicate that the CMV MCP lacks its own nuclear localization signal (NLS) and utilizes the pAP as an NLS-bearing escort into the nucleus. The CMV pAP amino acid sequence has two clusters of basic residues (e.g., KRRRER [NLS1] and KARKRLK [NLS2], for simian CMV) that resemble the simian virus 40 large-T-antigen NLS (D. Kalderon et al., Cell 39:499–509, 1984) and one of these (NLS1) has a counterpart in the pAP homologs of other herpesviruses. The work described here establishes that NLS1 and NLS2 are mutually independent NLS that can act (i) incisto translocate pAP and the related proteinase precursor (pNP1) into the nucleus and (ii) intransto transport MCP into the nucleus. By using combinations of NLS mutants and carboxy-terminal deletion constructs, we demonstrated a self-interaction of pAP and cytoplasmic interactions of pAP with pNP1 and of pNP1 with itself. The relevance of these findings to early steps in capsid assembly, the mechanism of MCP nuclear transport, and the possible cytoplasmic formation of protocapsomeric substructures is discussed.