Identification of a Minimal Region of the HIV-1 5′-Leader Required for RNA Dimerization, NC Binding, and Packaging

被引:85
作者
Heng, Xiao [2 ,3 ]
Kharytonchyk, Siarhei [1 ]
Garcia, Eric L. [1 ]
Lu, Kun [2 ,3 ]
Divakaruni, Sai Sachin [2 ,3 ]
LaCotti, Courtney [2 ,3 ]
Edme, Kedy [2 ,3 ]
Telesnitsky, Alice [1 ]
Summers, Michael F. [2 ,3 ]
机构
[1] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA
[2] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA
[3] Univ Maryland Baltimore Cty, Howard Hughes Med Inst, Baltimore, MD 21250 USA
关键词
retrovirus assembly; diploid genome packaging; RNA structure; ITC; nucleocapsid protein; HUMAN-IMMUNODEFICIENCY-VIRUS; MOLONEY MURINE LEUKEMIA; SARCIN RICIN LOOP; NUCLEOCAPSID PROTEIN; REVERSE TRANSCRIPTION; STEM-LOOP; SECONDARY STRUCTURE; VIRAL-RNA; STRUCTURAL FEATURES; GENOME DIMERIZATION;
D O I
10.1016/j.jmb.2012.01.033
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Assembly of human immunodeficiency virus type 1 (HIV-1) particles is initiated in the cytoplasm by the formation of a ribonucleoprotein complex comprising the dimeric RNA genome and a small number of viral Gag polyproteins. Genomes are recognized by the nucleocapsid (NC) domains of Gag, which interact with packaging elements believed to be located primarily within the 5'-leader (5'-L) of the viral RNA. Recent studies revealed that the native 5'-L exists as an equilibrium of two conformers, one in which dimer-promoting residues and NC binding sites are sequestered and packaging is attenuated, and one in which these sites are exposed and packaging is promoted. To identify the elements within the dimeric 5'-L that are important for packaging, we generated HIV-1 5'-L RNAs containing mutations and deletions designed to eliminate substructures without perturbing the overall structure of the leader and examined effects of the mutations on RNA dimerization, NC binding, and packaging. Our findings identify a 159-residue RNA packaging signal that possesses dimerization and NC binding properties similar to those of the intact 5'-L and contains elements required for efficient RNA packaging. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:224 / 239
页数:16
相关论文
共 120 条
[61]   Imaging the biogenesis of individual HIV-1 virions in live cells [J].
Jouvenet, Nolwenn ;
Bieniasz, Paul D. ;
Simon, Sanford M. .
NATURE, 2008, 454 (7201) :236-240
[62]   Imaging the interaction of HIV-1 genomes and Gag during assembly of individual viral particles [J].
Jouvenet, Nolwenn ;
Simon, Sanford M. ;
Bieniasz, Paul D. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (45) :19114-19119
[63]   A network of heterogeneous hydrogen bonds in GNRA tetraloops [J].
Jucker, FM ;
Heus, HA ;
Yip, PF ;
Moors, EHM ;
Pardi, A .
JOURNAL OF MOLECULAR BIOLOGY, 1996, 264 (05) :968-980
[64]   Recombination - Multiply infected spleen cells in HIV patients [J].
Jung, A ;
Maier, R ;
Vartanian, JP ;
Bocharov, G ;
Jung, V ;
Fischer, U ;
Meese, E ;
Wain-Hobson, S ;
Meyerhans, A .
NATURE, 2002, 418 (6894) :144-144
[65]   Specific interactions between HIV-1 nucleocapsid protein and the TAR element [J].
Kanevsky, I ;
Chaminade, F ;
Ficheux, D ;
Moumen, A ;
Gorelick, R ;
Negroni, M ;
Darlix, JL ;
Fossé, P .
JOURNAL OF MOLECULAR BIOLOGY, 2005, 348 (05) :1059-1077
[66]   RD-114, BABOON, AND WOOLLY MONKEY VIRAL RNAS COMPARED IN SIZE AND STRUCTURE [J].
KUNG, HJ ;
HU, S ;
BENDER, W ;
BAILEY, JM ;
DAVIDSON, N ;
NICOLSON, MO ;
MCALLISTER, RM .
CELL, 1976, 7 (04) :609-620
[67]   Dynamical behavior of the HIV-1 nucleocapsid protein [J].
Lee, BM ;
De Guzman, RN ;
Turner, BG ;
Tjandra, N ;
Summers, MF .
JOURNAL OF MOLECULAR BIOLOGY, 1998, 279 (03) :633-649
[68]  
Lever AML, 2007, ADV PHARMACOL, V55, P1, DOI 10.1016/S1054-3589(07)55001-5
[69]   NMR Detection of Structures in the HIV-1 5′-Leader RNA That Regulate Genome Packaging [J].
Lu, Kun ;
Heng, Xiao ;
Garyu, Lianko ;
Monti, Sarah ;
Garcia, Eric L. ;
Kharytonchyk, Siarhei ;
Dorjsuren, Bilguujin ;
Kulandaivel, Gowry ;
Jones, Simonne ;
Hiremath, Atheeth ;
Divakaruni, Sai Sachin ;
LaCotti, Courtney ;
Barton, Shawn ;
Tummillo, Daniel ;
Hosic, Azra ;
Edme, Kedy ;
Albrecht, Sara ;
Telesnitsky, Alice ;
Summers, Michael F. .
SCIENCE, 2011, 334 (6053) :242-245
[70]   Structural Determinants and Mechanism of HIV-1 Genome Packaging [J].
Lu, Kun ;
Heng, Xiao ;
Summers, Michael F. .
JOURNAL OF MOLECULAR BIOLOGY, 2011, 410 (04) :609-633