Structure of the HIV-1 RNA packaging signal

被引:220
作者
Keane, Sarah C. [1 ,2 ]
Heng, Xiao [1 ,2 ]
Lu, Kun [1 ,2 ]
Kharytonchyk, Siarhei [3 ]
Ramakrishnan, Venkateswaran [1 ,2 ]
Carter, Gregory [1 ,2 ]
Barton, Shawn [1 ,2 ]
Hosic, Azra [1 ,2 ]
Florwick, Alyssa [1 ,2 ]
Santos, Justin [1 ,2 ]
Bolden, Nicholas C. [1 ,2 ]
McCowin, Sayo [1 ,2 ]
Case, David A. [4 ]
Johnson, Bruce A. [5 ,6 ]
Salemi, Marco [7 ,8 ]
Telesnitsky, Alice [3 ]
Summers, Michael F. [1 ,2 ]
机构
[1] Univ Maryland Baltimore Cty, HHMI, Baltimore, MD 21250 USA
[2] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA
[3] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA
[4] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA
[5] One Moon Sci Inc, Westfield, NJ 07090 USA
[6] CUNY, Adv Sci Res Ctr, New York, NY 10031 USA
[7] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA
[8] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA
基金
美国国家科学基金会;
关键词
NUCLEOCAPSID PROTEIN; DIMERIZATION; BINDING; PSI; EFFICIENCY; REVEALS; GENOMES; REGION;
D O I
10.1126/science.aaa9266
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The 5' leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. By using a H-2-edited nuclear magnetic resonance (NMR) approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (core encapsidation signal; Psi(CES)). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions. The structure reveals how translation is attenuated, Gag binding promoted, and unspliced dimeric genomes selected, by the RNA conformer that directs packaging.
引用
收藏
页码:917 / 921
页数:5
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