The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity.
The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity.
复制标题
DOI：
10.1093/nar/gkab342
复制
发表时间：
2021-06-04
影响因子：
14.9
通讯作者：
Heng X
中科院分区：
文献类型：
--
作者：
Song Z;Gremminger T;Singh G;Cheng Y;Li J;Qiu L;Ji J;Lange MJ;Zuo X;Chen SJ;Zou X;Boris-Lawrie K;Heng X
HIV-1逆转录起始于病毒基因组RNA（gRNA）中的引物结合位点（PBS）。尽管PBS-区段的结构在tRNALys 3退火时经历实质性重排，但PBS-区段在gRNA包装期间的适当折叠是重要的，因为它确保了有益宿主因子的加载。DHX 9/RNA解旋酶A（RHA）被募集到gRNA以增强逆转录酶的持续合成能力。由于相互作用的分子细节尚未被定义，我们解决了优先由RHA结合的PBS-片段的溶液结构。结果表明，PBS片段采用了一种由引物激活茎（PAS）、tRNA样元件（TLE）和tRNA退火臂组成的富含腺苷的三向连接结构，破坏PBS片段的三向连接结构可减少逆转录产物，降低病毒的感染性。由于tRNA退火臂的存在，TLE和PAS形成弯曲的螺旋结构，其经历由RHA双链RNA结合结构域1（dsRBD 1）的形状依赖性识别。突变和系统发育分析提供的证据，PBS节段的三向连接结构，优先结合RHA支持有效的逆转录，HIV-1复制的标志性步骤的保护。
HIV-1 reverse transcription initiates at the primer binding site (PBS) in the viral genomic RNA (gRNA). Although the structure of the PBS-segment undergoes substantial rearrangement upon tRNALys3 annealing, the proper folding of the PBS-segment during gRNA packaging is important as it ensures loading of beneficial host factors. DHX9/RNA helicase A (RHA) is recruited to gRNA to enhance the processivity of reverse transcriptase. Because the molecular details of the interactions have yet to be defined, we solved the solution structure of the PBS-segment preferentially bound by RHA. Evidence is provided that PBS-segment adopts a previously undefined adenosine-rich three-way junction structure encompassing the primer activation stem (PAS), tRNA-like element (TLE) and tRNA annealing arm. Disruption of the PBS-segment three-way junction structure diminished reverse transcription products and led to reduced viral infectivity. Because of the existence of the tRNA annealing arm, the TLE and PAS form a bent helical structure that undergoes shape-dependent recognition by RHA double-stranded RNA binding domain 1 (dsRBD1). Mutagenesis and phylogenetic analyses provide evidence for conservation of the PBS-segment three-way junction structure that is preferentially bound by RHA in support of efficient reverse transcription, the hallmark step of HIV-1 replication.
登录
查看更多内容
影响因子：
14.9
作者：
Bou-Nader, Charles;Barraud, Pierre;Hamdane, Djemel
通讯作者：
Hamdane, Djemel
影响因子：
4.5
作者：
Cao, Song;Chen, Shi-Jie
通讯作者：
Chen, Shi-Jie
影响因子：
5.6
作者：
Damgaard, CK;Andersen, ES;Kjems, J
通讯作者：
Kjems, J
DOI：
10.1073/pnas.89.14.6472
发表时间：
1992-07-15
影响因子：
11.1
作者：
DEROCQUIGNY, H;GABUS, C;DARLIX, JL
通讯作者：
DARLIX, JL
影响因子：
4.8
作者：
Brady, Samantha;Singh, Gatikrushna;Heng, Xiao
通讯作者：
Heng, Xiao