NMR structure of the mature dimer initiation complex of HIV‐1 genomic RNA

Mujeeb, Anwer; Parslow, Tristram G.; Zarrinpar, Ali; Das, Chandreyee Manas; James, Thomas Leroy

doi:10.1016/s0014-5793(99)01183-7

Cited by 51 publications

(36 citation statements)

References 20 publications

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“…As an application of the model, we will study the energy landscape of the HIV-1 dimerization initiation signal (DIS), which shows the kissing-loop dimer and the extended-duplex dimer coexisting in thermal equilibrium. The theoretical predictions are consistent with the two forms of RNA-RNA complexes observed in crystal and NMR structural measurements (Mujeeb et al 1998(Mujeeb et al , 1999Ennifar et al 1999Ennifar et al , 2001Takahashi et al 2005;Ulyanov et al 2006).…”

Section: Introductionsupporting

confidence: 82%

Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal

Cao¹,

Chen²

2011

RNA

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We develop a statistical mechanical model to predict the structure and folding stability of the RNA/RNA kissing-loop complex. One of the key ingredients of the theory is the conformational entropy for the RNA/RNA kissing complex. We employ the recently developed virtual bond-based RNA folding model (Vfold model) to evaluate the entropy parameters for the different types of kissing loops. A benchmark test against experiments suggests that the entropy calculation is reliable. As an application of the model, we apply the model to investigate the structure and folding thermodynamics for the kissing complex of the HIV-1 dimerization initiation signal. With the physics-based energetic parameters, we compute the free energy landscape for the HIV-1 dimer. From the energy landscape, we identify two minimal free energy structures, which correspond to the kissing-loop dimer and the extended-duplex dimer, respectively. The results support the two-step dimerization process for the HIV-1 replication cycle. Furthermore, based on the Vfold model and energy minimization, the theory can predict the native structure as well as the local minima in the free energy landscape. The root-mean-square deviations (RMSDs) for the predicted kissing-loop dimer and extended-duplex dimer are~3.0 Å . The method developed here provides a new method to study the RNA/RNA kissing complex.

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Section: Introductionsupporting

confidence: 82%

Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal

Cao¹,

Chen²

2011

RNA

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“…In these complexes, base complementarity exists not only between the intermolecular hairpin loops, but also between the stem regions. In the case of the dimer initiation complex of the HIV-genomic RNA, a metastable intermolecular kissing interaction culminates in a linear duplex isoform stabilized by intermolecular base pairing (20,44). A kissing interaction also initiates the binding of the antisense RNA CopA to its target, CopT, but the outcome of this interaction is an unusual four-way junction defined by the predicted base stacking arrangements of intramolecular helices and newly formed intermolecular helices (19,45).…”

Section: Discussionmentioning

confidence: 99%

“…Kissing complexes in which the loop nucleotides are complementary can form stable dimers that contain intermolecular base pairs between the loop nucleotides only. Other stem-loops with more extensive complementarity sometimes form unstable kissing complexes, which are quickly remodeled into stable duplex or cruciform isoforms (18)(19)(20). Secondary structure remodeling involves breaking intramolecular base pairs in each hairpin and using the bases to form intermolecular helices.…”

mentioning

confidence: 99%

Intramolecular secondary structure rearrangement by the kissing interaction of the Neurospora VS ribozyme

Andersen

Collins

2001

Proc. Natl. Acad. Sci. U.S.A.

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Kissing interactions in RNA are formed when bases between two hairpin loops pair. Intra-and intermolecular kissing interactions are important in forming the tertiary or quaternary structure of many RNAs. Self-cleavage of the wild-type Varkud satellite (VS) ribozyme requires a kissing interaction between the hairpin loops of stemloops I and V. In addition, self-cleavage requires a rearrangement of several base pairs at the base of stem I. We show that the kissing interaction is necessary for the secondary structure rearrangement of wild-type stem-loop I. Surprisingly, isolated stem-loop V in the absence of the rest of the ribozyme is sufficient to rearrange the secondary structure of isolated stem-loop I. In contrast to kissing interactions in other RNAs that are either confined to the loops or culminate in an extended intermolecular duplex, the VS kissing interaction causes changes in intramolecular base pairs within the target stem-loop.R NA kissing interactions, also called loop-loop pseudoknots, occur when the unpaired nucleotides in one hairpin loop base pair with the unpaired nucleotides in another hairpin loop (1). When the hairpin loops are located on separate RNA molecules, their intermolecular interaction is called a kissing complex. These interactions generally form between stem-loops containing extensive complementarity; however, stable complexes have been observed containing only two intermolecular Watson-Crick base pairs (2).Intramolecular kissing interactions are observed in the native structures of a variety of RNAs including Varkud satellite (VS) RNA, tRNA, and group I introns (3-6). These kissing interactions contribute to the assembly and stabilization of their respective RNA structures by joining and orienting helices. Kissing interactions may stabilize both native and nonnative interactions during tertiary folding, which can affect the rate at which the native structure is formed (7). Kissing interactions often form distorted structures that can serve as recognition sites for proteins, RNAs, metal ions, or other ligands (8-10). As a result, kissing interactions contribute to the stability of an RNA structure by affecting both global and local RNA interactions.The transient formation of an intermolecular kissing complex is required for RNA dimerization during the life cycle of retroviruses (11-15), and for the formation of some antisensetarget complexes (16,17). Kissing complexes in which the loop nucleotides are complementary can form stable dimers that contain intermolecular base pairs between the loop nucleotides only. Other stem-loops with more extensive complementarity sometimes form unstable kissing complexes, which are quickly remodeled into stable duplex or cruciform isoforms (18)(19)(20). Secondary structure remodeling involves breaking intramolecular base pairs in each hairpin and using the bases to form intermolecular helices.The VS ribozyme contains a kissing interaction that is required for self-cleavage of the wild-type RNA in vitro (6). This interaction involves Watson-Crick bas...

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“…These latter changes may either affect the appropriate presentation of the palindrome within the loop, which is needed to initiate RNA dimerization, or prevent the transition of RNA dimers from the loose to the stable form. Detailed structures of the RNA dimer formed by SL1 have shown that both loop and stem sequences contribute to stabilization of the RNA duplex (11,12,14,35,36,49). As an example, the loop region contains three adenine residues that cannot form base pairs within the dimer and, as a consequence, might be expected to distort the RNA duplex.…”

mentioning

confidence: 99%

Effects of a Single Amino Acid Substitution within thep2 Region of Human Immunodeficiency Virus Type 1 on Packagingof Spliced ViralRNA

Russell

Roldán

Detorio

et al. 2003

J Virol

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Human immunodeficiency virus type 1 encapsidates two copies of viral genomic RNA in the form of a dimer. The dimerization process initiates via a 6-nucleotide palindrome that constitutes the loop of a viral RNA stem-loop structure (i.e., stem loop 1 [SL1], also termed the dimerization initiation site [DIS]) located within the 5 untranslated region of the viral genome. We have now shown that deletion of the entire DIS sequence virtually eliminated viral replication but that this impairment was overcome by four second-site mutations located within the matrix (MA), capsid (CA), p2, and nucleocapsid (NC) regions of Gag. Interestingly, defective viral RNA dimerization caused by the ⌬DIS deletion was not significantly corrected by these compensatory mutations, which did, however, allow the mutated viruses to package wild-type levels of this DIS-deleted viral RNA while excluding spliced viral RNA from encapsidation. Further studies demonstrated that the compensatory mutation T12I located within p2, termed MP2, sufficed to prevent spliced viral RNA from being packaged into the ⌬DIS virus. Consistently, the ⌬DIS-MP2 virus displayed significantly higher levels of infectiousness than did the ⌬DIS virus. The importance of position T12 in p2 was further demonstrated by the identification of four point mutations,T12D, T12E, T12G, and T12P, that resulted in encapsidation of spliced viral RNA at significant levels. Taken together, our data demonstrate that selective packaging of viral genomic RNA is influenced by the MP2 mutation and that this represents a major mechanism for rescue of viruses containing the ⌬DIS deletion.

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NMR structure of the mature dimer initiation complex of HIV‐1 genomic RNA

Cited by 51 publications

References 20 publications

Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal

Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal

Intramolecular secondary structure rearrangement by the kissing interaction of the Neurospora VS ribozyme

Effects of a Single Amino Acid Substitution within thep2 Region of Human Immunodeficiency Virus Type 1 on Packagingof Spliced ViralRNA

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