Formation of immature and mature genomic RNA dimers in wild-type and protease-inactive HIV-1: Differential roles of the Gag polyprotein, nucleocapsid proteins NCp15, NCp9, NCp7, and the dimerization initiation site
Formation of immature and mature genomic RNA dimers in wild-type and protease-inactive HIV-1: Differential roles of the Gag polyprotein, nucleocapsid proteins NCp15, NCp9, NCp7, and the dimerization initiation site
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DOI：
10.1016/j.virol.2010.08.013
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发表时间：
2010-11-25
期刊：
影响因子：
3.7
通讯作者：
Laughrea, Michael
中科院分区：
文献类型：
--
作者：
Jalalirad, Mohammad;Laughrea, Michael
不成熟基因组RNA（gRNA）二聚体的形成在蛋白酶失活（PR-in）HIV-1中是精确依赖于核衣壳（NC）的。这确定了Pr 55 gag/Pr 160 gag-pol在完整的HIV-1内具有NC依赖性伴侣活性。Pr 55 gag/Pr 160 gag-pol的NC序列的近端锌指和接头中的突变消除了HIV-1中PR-中的gRNA二聚化。在野生型中，Pr 55 gag的NC被加工成逐渐变小的蛋白质，称为NCp 15（NCp 7-p1-p6）、NCp 9（NCp 7-p1）和NCp 7，未成熟二聚体的形成比HIV-1中的PR-更快。NCp 7和NCp 15指导这种快速积累。NCp 9在该过程中是缓慢的，但它与NCp 7一样刺激从不成熟到成熟gRNA二聚体的转变，并且比NCp 15好得多。氨基末端，近端锌指，接头。和远端锌指的NCp 7有助于这一成熟事件在完整的HIV-1。DIS是所有未成熟gRNA二聚体的二聚化起始位点，无论其形成机制如何。(C)2010年爱思唯尔公司All rights reserved.
Formation of immature genomic RNA (gRNA) dimers is exquisitely nucleocapsid (NC)-dependent in protease-inactive (PR-in) HIV-1. This establishes that Pr55gag/Pr160gag-pol has NC-dependent chaperone activity within intact HIV-1. Mutations in the proximal zinc finger and the linker of the NC sequence of Pr55gag/Pr160gag-pol abolish gRNA dimerization in PR-in HIV-1. In wild type, where the NC of Pr55gag is processed into progressively smaller proteins termed NCp15 (NCp7-p1-p6), NCp9 (NCp7-p1) and NCp7, formation of immature dimers is much swifter than in PR-in HIV-1. NCp7 and NCp15 direct this rapid accumulation. NCp9 is sluggish in this process, but it stimulates the transition from immature to mature gRNA dimer as well as NCp7 and much better than NCp15. The amino-terminus, proximal zinc finger, linker. and distal zinc finger of NCp7 contribute to this maturation event in intact HIV-1. The DIS is a dimerization initiation site for all immature gRNA dimers, irrespective of their mechanism of formation. (C) 2010 Elsevier Inc. All rights reserved.