The major HIV-1 packaging signal is an extended bulged stem loop whose structure is altered on interaction with the gag polyprotein

2000 ◽  
Vol 301 (5) ◽  
pp. 1315
Author(s):  
Amanda Zeffman ◽  
Stuart Hassard ◽  
Gabriele Varani ◽  
Andrew Lever
Keyword(s):  
Packaging Signal ◽  
Stem Loop ◽  
Gag Polyprotein ◽  
Hiv 1

scholarly journals The Zinc Content of HIV-1 NCp7 Affects Its Selectivity for Packaging Signal and Affinity for Stem-Loop 3

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1922
Author(s):  
Ying Wang ◽  
Chao Guo ◽  
Xing Wang ◽  
Lianmei Xu ◽  
Rui Li ◽  
...  
Keyword(s):  
Rna Binding ◽  
Zinc Content ◽  
Binding Property ◽  
Zinc Ions ◽  
Packaging Signal ◽  
Stem Loop ◽  
Virus Maturation ◽  
Gag Polyprotein ◽  
Zinc Finger Motifs ◽  
Hiv 1

The nucleocapsid (NC) protein of human immunodeficiency (HIV) is a small, highly basic protein containing two CCHC zinc-finger motifs, which is cleaved from the NC domain of the Gag polyprotein during virus maturation. We previously reported that recombinant HIV-1 Gag and NCp7 overexpressed in an E. coli host contains two and one zinc ions, respectively, and Gag exhibited much higher selectivity for packaging signal (Psi) and affinity for the stem-loop (SL)-3 of Psi than NCp7. In this study, we prepared NCp7 containing 0 (0NCp7), 1 (NCp7) or 2 (2NCp7) zinc ions, and compared their secondary structure, Psi-selectivity and SL3-affinity. Along with the decrease of the zinc content, less ordered conformations were detected. Compared to NCp7, 2NCp7 exhibited a much higher Psi-selectivity and SL3-affinity, similar to Gag, whereas 0NCp7 exhibited a lower Psi-selectivity and SL3-affinity, similar to the H23&H44K double mutant of NCp7, indicating that the different RNA-binding property of Gag NC domain and the mature NCp7 may be resulted, at least partially, from their different zinc content. This study will be helpful to elucidate the critical roles that zinc played in the viral life cycle, and benefit further investigations of the functional switch from the NC domain of Gag to the mature NCp7.

ANTIVIRAL ACTIVITY OF STERIC-BLOCK OLIGONUCLEOTIDES TARGETING THE HIV-1 TRANS-ACTIVATION RESPONSE AND PACKAGING SIGNAL STEM-LOOP RNAS

2005 ◽  
Vol 24 (5-7) ◽  
pp. 393-396 ◽  
Author(s):  
Douglas Brown ◽  
Andrey A. Arzumanov ◽  
John J. Turner ◽  
Dmitry A. Stetsenko ◽  
Andrew M. L. Lever ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Packaging Signal ◽  
Stem Loop ◽  
Activation Response ◽  
Hiv 1

Stem-loop SL4 of the HIV-1 Ψ RNA packaging signal exhibits weak affinity for the nucleocapsid protein. structural studies and implications for genome recognition

2001 ◽  
Vol 314 (5) ◽  
pp. 961-970 ◽  
Author(s):  
Gaya K. Amarasinghe ◽  
Jing Zhou ◽  
Matthew Miskimon ◽  
Kalola J. Chancellor ◽  
Jasmine A. McDonald ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Structural Studies ◽  
Rna Packaging ◽  
Packaging Signal ◽  
Stem Loop ◽  
Genome Recognition ◽  
Rna Packaging Signal ◽  
Hiv 1

scholarly journals HIV-1 Packaging Visualised by In-Gel SHAPE

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2389
Author(s):  
Aaron R. D’Souza ◽  
Dhivya Jayaraman ◽  
Ziqi Long ◽  
Jingwei Zeng ◽  
Liam J. Prestwood ◽  
...  
Keyword(s):  
Rna Structure ◽  
Structural Changes ◽  
Structural Protein ◽  
Packaging Signal ◽  
Packaging Process ◽  
Gag Polyprotein ◽  
Rna Conformation ◽  
Shape Selective ◽  
Insight Into ◽  
Hiv 1

HIV-1 packages two copies of its gRNA into virions via an interaction with the viral structural protein Gag. Both copies and their native RNA structure are essential for virion infectivity. The precise stepwise nature of the packaging process has not been resolved. This is largely due to a prior lack of structural techniques that follow RNA structural changes within an RNA–protein complex. Here, we apply the in-gel SHAPE (selective 2’OH acylation analysed by primer extension) technique to study the initiation of HIV-1 packaging, examining the interaction between the packaging signal RNA and the Gag polyprotein, and compare it with that of the NC domain of Gag alone. Our results imply interactions between Gag and monomeric packaging signal RNA in switching the RNA conformation into a dimerisation-competent structure, and show that the Gag–dimer complex then continues to stabilise. These data provide a novel insight into how HIV-1 regulates the translation and packaging of its genome.

NMR structure of stem-loop SL2 of the HIV-1 Ψ RNA packaging signal reveals a novel A-U-A base-triple platform 1 1Edited by I. Tinoco

2000 ◽  
Vol 299 (1) ◽  
pp. 145-156 ◽  
Author(s):  
Gaya K Amarasinghe ◽  
Roberto N De Guzman ◽  
Ryan B Turner ◽  
Michael F Summers
Keyword(s):  
Nmr Structure ◽  
Rna Packaging ◽  
Packaging Signal ◽  
Stem Loop ◽  
Rna Packaging Signal ◽  
Hiv 1

NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the Ψ-RNA packaging signal. implications for genome recognition 1 1Edited by P. Wright

2000 ◽  
Vol 301 (2) ◽  
pp. 491-511 ◽  
Author(s):  
Gaya K Amarasinghe ◽  
Roberto N De Guzman ◽  
Ryan B Turner ◽  
Kalola J Chancellor ◽  
Zeng Rong Wu ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nmr Structure ◽  
Rna Packaging ◽  
Packaging Signal ◽  
Stem Loop ◽  
Genome Recognition ◽  
Rna Packaging Signal ◽  
Hiv 1

scholarly journals The nucleic acid chaperone activity of the HIV-1 Gag polyprotein is boosted by its cellular partner RPL7: a kinetic study

2020 ◽  
Vol 48 (16) ◽  
pp. 9218-9234
Author(s):  
Hassan Karnib ◽  
Muhammad F Nadeem ◽  
Nicolas Humbert ◽  
Kamal K Sharma ◽  
Natalia Grytsyk ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Kinetic Study ◽  
Viral Assembly ◽  
Chaperone Activity ◽  
Stem Loop ◽  
Gag Protein ◽  
Gag Polyprotein ◽  
Nucleic Acid Chaperone ◽  
Cellular Partner ◽  
Hiv 1

Abstract The HIV-1 Gag protein playing a key role in HIV-1 viral assembly has recently been shown to interact through its nucleocapsid domain with the ribosomal protein L7 (RPL7) that acts as a cellular co-factor promoting Gag's nucleic acid (NA) chaperone activity. To further understand how the two proteins act together, we examined their mechanism individually and in concert to promote the annealing between dTAR, the DNA version of the viral transactivation element and its complementary cTAR sequence, taken as model HIV-1 sequences. Gag alone or complexed with RPL7 was found to act as a NA chaperone that destabilizes cTAR stem-loop and promotes its annealing with dTAR through the stem ends via a two-step pathway. In contrast, RPL7 alone acts as a NA annealer that through its NA aggregating properties promotes cTAR/dTAR annealing via two parallel pathways. Remarkably, in contrast to the isolated proteins, their complex promoted efficiently the annealing of cTAR with highly stable dTAR mutants. This was confirmed by the RPL7-promoted boost of the physiologically relevant Gag-chaperoned annealing of (+)PBS RNA to the highly stable tRNALys3 primer, favoring the notion that Gag recruits RPL7 to overcome major roadblocks in viral assembly.

scholarly journals Potential Achilles heels of SARS-CoV-2 displayed by the base order-dependent component of RNA folding energy

2020 ◽  
Author(s):  
Chiyu Zhang ◽  
Donald R. Forsdyke
Keyword(s):  
Rna Structure ◽  
Folding Energy ◽  
Packaging Signal ◽  
Antiviral Compound ◽  
N Protein ◽  
Gag Polyprotein ◽  
Protein Encoding ◽  
Dependent Component ◽  
High Base ◽  
Hiv 1

ABSTRACTBase order, not composition, best reflects local evolutionary pressure for folding of single-stranded nucleic acids. The base order-dependent component of folding energy has revealed a highly conserved region in HIV-1 genomes that associates with RNA structure. This corresponds to a packaging signal that is recognized by the nucleocapsid domain of the Gag polyprotein. Long viewed as a potential HIV-1 “Achilles heel,” the signal can be targeted by a recently described antiviral compound (NSC 260594) or by synthetic oligonucleotides. Thus, a conserved base-order-rich region of HIV-1 may facilitate therapeutic attack. Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. This indicates structural invariance (SI) sustained by natural selection. While the regions are often also protein-encoding (e.g. NSP3, ORF3a), we suggest that their nucleic acid level functions – such as the ribosomal frameshifting element (FSE) that facilitates differential expression of 1a and 1ab polyproteins – can be considered potential “Achilles heels” for SARS-CoV-2, perhaps susceptible to therapies like those envisaged for AIDS. The region of the FSE scored well, but higher SI scores were obtained in other regions, including those encoding NSP13 and the nucleocapsid (N) protein.

scholarly journals Structure, Function, and Interactions of the HIV-1 Capsid Protein

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 100
Author(s):  
Eric Rossi ◽  
Megan E. Meuser ◽  
Camille J. Cunanan ◽  
Simon Cocklin
Keyword(s):  
Life Cycle ◽  
Capsid Protein ◽  
Adaptor Proteins ◽  
Restriction Factors ◽  
Gag Polyprotein ◽  
Immunodeficiency Virus ◽  
Host Cell Factors ◽  
Hiv 1

The capsid (CA) protein of the human immunodeficiency virus type 1 (HIV-1) is an essential structural component of a virion and facilitates many crucial life cycle steps through interactions with host cell factors. Capsid shields the reverse transcription complex from restriction factors while it enables trafficking to the nucleus by hijacking various adaptor proteins, such as FEZ1 and BICD2. In addition, the capsid facilitates the import and localization of the viral complex in the nucleus through interaction with NUP153, NUP358, TNPO3, and CPSF-6. In the later stages of the HIV-1 life cycle, CA plays an essential role in the maturation step as a constituent of the Gag polyprotein. In the final phase of maturation, Gag is cleaved, and CA is released, allowing for the assembly of CA into a fullerene cone, known as the capsid core. The fullerene cone consists of ~250 CA hexamers and 12 CA pentamers and encloses the viral genome and other essential viral proteins for the next round of infection. As research continues to elucidate the role of CA in the HIV-1 life cycle and the importance of the capsid protein becomes more apparent, CA displays potential as a therapeutic target for the development of HIV-1 inhibitors.

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