To prime reverse transcription, retroviruses require annealing of a transfer RNA molecule to the U5 primer binding site (U5-PBS) region of the viral genome1,2. The residues essential for primer annealing are initially locked in intramolecular interactions3,4,5; hence, annealing requires the chaperone activity of the retroviral nucleocapsid (NC) protein to facilitate structural rearrangements6. Here we show that, unlike classical chaperones, the Moloney murine leukaemia virus NC uses a unique mechanism for remodelling: it specifically targets multiple structured regions in both the U5-PBS and tRNAPro primer that otherwise sequester residues necessary for annealing. This high-specificity and high-affinity binding by NC consequently liberates these sequestered residues—which are exactly complementary—for intermolecular interactions. Furthermore, NC utilizes a step-wise, entropy-driven mechanism to trigger both residue-specific destabilization and residue-specific release. Our structures of NC bound to U5-PBS and tRNAPro reveal the structure-based mechanism for retroviral primer annealing and provide insights as to how ATP-independent chaperones can target specific RNAs amidst the cellular milieu of non-target RNAs.
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Harada, F., Peters, G. G. & Dahlberg, J. E. The primer tRNA for Moloney murine leukemia virus DNA synthesis. Nucleotide sequence and aminoacylation of tRNAPro. J. Biol. Chem. 254, 10979–10985 (1979)
Wain-Hobson, S., Sonigo, P., Danos, O., Cole, S. & Alizon, M. Nucleotide sequence of the AIDS virus, LAV. Cell 40, 9–17 (1985)
Mougel, M. et al. Conformational analysis of the 5′ leader and the gag initiation site of Mo-MuLV RNA and allosteric transitions induced by dimerization. Nucleic Acids Res. 21, 4677–4684 (1993)
Paillart, J. C. et al. First snapshots of the HIV-1 RNA structure in infected cells and in virions. J. Biol. Chem. 279, 48397–48403 (2004)
Wilkinson, K. A. et al. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states. PLoS Biol. 6, e96 (2008)
Levin, J. G., Mitra, M., Mascarenhas, A. & Musier-Forsyth, K. Role of HIV-1 nucleocapsid protein in HIV-1 reverse transcription. RNA Biol. 7, 754–774 (2010)
Cordell, B., Stavnezer, E., Friedrich, R., Bishop, J. M. & Goodman, H. M. Nucleotide sequence that binds primer for DNA synthesis to the avian sarcoma virus genome. J. Virol. 19, 548–558 (1976)
Beerens, N., Groot, F. & Berkhout, B. Initiation of HIV-1 reverse transcription is regulated by a primer activation signal. J. Biol. Chem. 276, 31247–31256 (2001)
Beerens, N. & Berkhout, B. Switching the in vitro tRNA usage of HIV-1 by simultaneous adaptation of the PBS and PAS. RNA 8, 357–369 (2002)
Thomas, J. A. & Gorelick, R. J. Nucleocapsid protein function in early infection processes. Virus Res. 134, 39–63 (2008)
Rein, A. Nucleic acid chaperone activity of retroviral Gag proteins. RNA Biol. 7, 700–705 (2010)
Woodson, S. A. Taming free energy landscapes with RNA chaperones. RNA Biol. 7, 677–686 (2010)
De Rocquigny, H. et al. Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers. Proc. Natl Acad. Sci. USA 89, 6472–6476 (1992)
Hargittai, M. R., Mangla, A. T., Gorelick, R. J. & Musier-Forsyth, K. HIV-1 nucleocapsid protein zinc finger structures induce tRNALys,3 structural changes but are not critical for primer/template annealing. J. Mol. Biol. 312, 985–997 (2001)
Prats, A. C. et al. Viral RNA annealing activities of the nucleocapsid protein of Moloney murine leukemia virus are zinc independent. Nucleic Acids Res. 19, 3533–3541 (1991)
Rein, A., Henderson, L. E. & Levin, J. G. Nucleic-acid-chaperone activity of retroviral nucleocapsid proteins: significance for viral replication. Trends Biochem. Sci. 23, 297–301 (1998)
Tamura, M. & Holbrook, S. R. Sequence and structural conservation in RNA ribose zippers. J. Mol. Biol. 320, 455–474 (2002)
Nonin-Lecomte, S., Felden, B. & Dardel, F. NMR structure of the Aquifex aeolicus tmRNA pseudoknot PK1: new insights into the recoding event of the ribosomal trans-translation. Nucleic Acids Res. 34, 1847–1853 (2006)
D’Souza, V. & Summers, M. F. Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus. Nature 431, 586–590 (2004)
Dey, A., York, D., Smalls-Mantey, A. & Summers, M. F. Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus. Biochemistry 44, 3735–3744 (2005)
D’Souza, V. et al. Identification of a high affinity nucleocapsid protein binding element within the Moloney murine leukemia virus ψ-RNA packaging signal: implications for genome recognition. J. Mol. Biol. 314, 217–232 (2001)
Theimer, C. A., Finger, L. D. & Feigon, J. YNMG tetraloop formation by a dyskeratosis congenita mutation in human telomerase RNA. RNA 9, 1446–1455 (2003)
de Smit, M. H. et al. Structural variation and functional importance of a D-loop–T-loop interaction in valine-accepting tRNA-like structures of plant viral RNAs. Nucleic Acids Res. 30, 4232–4240 (2002)
Martin-Tumasz, S., Richie, A. C., Clos, L. J., II, Brow, D. A. & Butcher, S. E. A novel occluded RNA recognition motif in Prp24 unwinds the U6 RNA internal stem loop. Nucleic Acids Res. 39, 7837–7847 (2011)
Gonsky, J., Bacharach, E. & Goff, S. P. Identification of residues of the Moloney murine leukemia virus nucleocapsid critical for viral DNA synthesis in vivo. J. Virol. 75, 2616–2626 (2001)
Liu, S., Harada, B. T., Miller, J. T., Le Grice, S. F. & Zhuang, X. Initiation complex dynamics direct the transitions between distinct phases of early HIV reverse transcription. Nature Struct. Mol. Biol. 17, 1453–1460 (2010)
Fedorova, O., Solem, A. & Pyle, A. M. Protein-facilitated folding of group II intron ribozymes. J. Mol. Biol. 397, 799–813 (2010)
Semrad, K. Proteins with RNA chaperone activity: a world of diverse proteins with a common task-impediment of RNA misfolding. Biochem. Res. Int. 2011, 532908 (2011)
Dethoff, E. A., Chugh, J., Mustoe, A. M. & Al-Hashimi, H. M. Functional complexity and regulation through RNA dynamics. Nature 482, 322–330 (2012)
Adachi, A. et al. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J. Virol. 59, 284–291 (1986)
Miller, J. T., Khvorova, A., Scaringe, S. A. & Le Grice, S. F. Synthetic tRNALys,3 as the replication primer for the HIV-1HXB2 and HIV-1Mal genomes. Nucleic Acids Res. 32, 4687–4695 (2004)
Hansen, M. R., Mueller, L. & Pardi, A. Tunable alignment of macromolecules by filamentous phage yields dipolar coupling interactions. Nature Struct. Biol. 5, 1065–1074 (1998)
D’Souza, V., Dey, A., Habib, D. & Summers, M. F. NMR structure of the 101-nucleotide core encapsidation signal of the Moloney murine leukemia virus. J. Mol. Biol. 337, 427–442 (2004)
Spriggs, S., Garyu, L., Connor, R. & Summers, M. F. Potential intra- and intermolecular interactions involving the unique-5′ region of the HIV-1 5′-UTR. Biochemistry 47, 13064–13073 (2008)
Pizzato, M. et al. A one-step SYBR Green I-based product-enhanced reverse transcriptase assay for the quantitation of retroviruses in cell culture supernatants. J. Virol. Methods 156, 1–7 (2009)
Auerbach, M. R., Shu, C., Kaplan, A. & Singh, I. R. Functional characterization of a portion of the Moloney murine leukemia virus gag gene by genetic footprinting. Proc. Natl Acad. Sci. USA 100, 11678–11683 (2003)
Lim, D., Orlova, M. & Goff, S. P. Mutations of the RNase H C helix of the Moloney murine leukemia virus reverse transcriptase reveal defects in polypurine tract recognition. J. Virol. 76, 8360–8373 (2002)
Onafuwa-Nuga, A. A., King, S. R. & Telesnitsky, A. Nonrandom packaging of host RNAs in moloney murine leukemia virus. J. Virol. 79, 13528–13537 (2005)
We wish to thank the laboratory of S. Goff for the pNCS plasmid, C. Salguero for the artistic rendition of the model, as well as M. Summers and R. Gaudet for critical reading of the manuscript and the Merck Research Fellowship and Damon Runyon Cancer Research scholarship for funding.
The authors declare no competing financial interests.
Extended data figures and tables
Extended Data Figure 1 Specific, higher-affinity interactions of MLV NC with monomeric MLV U5-PBS and tRNAPro and its implications.
a, MLV NC sequence depicting the zinc finger moiety with amino- and carboxy-terminal tails. b, Cartoon representation displaying the general mechanism of ATP-independent chaperones. c, Cartoon representation of the E- and B-forms of U5-PBS genomic RNA, including the secondary structure of the Ψ-genome packaging signal, with the high-affinity sites coloured in red (see Supplementary Discussion 1). d, ITC data for MLV NC binding to native U5-PBS-B (black) and site 1 mutant (V1M, red) forms. Top, raw ITC data for 1.5 µl titrations of 80 µM NC into 5 µM RNA at 30 °C. Bottom, data following peak integration, with continuous black line representing the fit for a one-site binding model. Elimination of site V1 in the U5-PBS B-form completely abolishes the binding. e, f, ITC data showing weak binding of HIV NC to HIV U5-PBS RNA and tRNALys 3 primer. g, Portions of two-dimensional NOESY spectra collected in D2O displaying an overlay of free tRNALys 3 primer (black) and 0.5 equivalents of MLV NC (red). Lack of any chemical shift perturbation indicates the absence of any interactions between the two molecules. h, Models for primer annealing in MLV and HIV-1: in MLV (left), high-affinity binding of the NC domain (red) of Gag to the U5-PBS region of the viral genome and to the tRNAPro primer promotes tRNA annealing in the cytosol of the host cell before virion budding. Further supporting this model is the evidence that MLV virions are only slightly enriched for the tRNAPro primer (see Supplementary Discussion 1). In HIV-1 (right), NC does not bind with high affinity to the U5-PBS domain or to the primer tRNALys 3. Furthermore, the tRNALys 3 primer is highly enriched in HIV-1 virions (see Supplementary Discussion 1), which leads to primer annealing after virion budding, mediated by weak, non-specific interactions of HIV-1 NC with the viral and primer RNAs. For the sake of simplicity, only one of the two packaged retroviral genome copies is shown.
a, Top, portion of the 1H–1H two-dimensional NOESY spectrum showing imino-to-imino NOEs for the U5-PBS RNA. Data were collected at 10 °C in 10 mM NaCl and 10 mM Tris (pH 5.0). Imino-to-imino connectivities for the upper stem are shown in orange, while those for the lower stem are shown in blue. Inset, secondary structure of the U5-PBS construct used for structural and biochemical studies. Grey residues indicate non-native positions: the G96C:C157G base pair represents a base-pair swap alteration that was made to aid in unambiguous assignments of the otherwise five consecutive Gs and the terminal G–C base pair was added for the purposes of transcriptional efficiency and for SmaI digestion of the DNA template. Bottom, portions of the 1H–15N two-dimensional HSQC spectra for 15N, 13C-labelled U5-PBS. The imino resonances for U- and G-labelled samples are shown, as are amino resonances for the A-labelled sample. The A98 amino resonances had unusually downfield chemical shifts due to interaction with the G155 inside the helix. Formation of the stacking interactions of G155 is shown on the right with a zoom-in inset. The stacking is also confirmed by a G155 to U156 walk in the D2O two-dimensional NOESY spectrum (data not shown). b, Portion of the 1H–1H two-dimensional NOESY imino spectrum overlay for U5-PBS constructs with and without the G96C:C157G base-pair swap. No change in the imino-to-imino connectivities were observed for the RNA except at the expected mutation site (shown in boxed region). In fact, the GA98, GU156 bulge immediately above the G–C swap has the exact chemical shifts, line widths and so on in both constructs, demonstrating that they have similar secondary structures. Importantly, similar binding affinities with the NC protein were obtained for both constructs. c, U5-PBS NMR ensemble alignments: the ensemble of the lowest-energy AMBER structures is shown. They are aligned by the top portion (left) or bottom portion (right) of the molecule. NC binding sites V1 (UCUG110) and V2 (UCAG130) are shown in red and orange, respectively. Left, alignment of residues 112–125 and 132–144, yielding a root mean squared deviation (r.m.s.d.) value of 0.6 ± 0.2 Å. Right, alignment of residues 94–106 and 147–159, excluding G155, which appears from NOE data to exhibit multiple conformations. The resulting r.m.s.d. for alignment of the bottom residues is 1.2 ± 0.5 Å.
a, Three-dimensional NOESY-HMQC strip plot of the 13C-edited 1H–1H planes for C128 and A129 aromatic and H1′ protons. NOEs from A129 H8 to the preceding C128 ribose protons are indicative of stacking interaction between the two residues. In contrast, the minor conformation that is populated upon NC binding does not give rise to any inter-residue NOEs (data not shown). b, Structure of the UCAG tetraloop. The U–G hydrogen bonds, characteristic of UNCG tetraloops, are shown in green. c, Lack of NOEs between U121 and A122 indicate a break in regular stacking interactions between these two residues. Strip plots of 13C-edited 1H–1H planes for U121 H2′ and A122 H2 from three-dimensional NOESY-HMQC spectra are shown. The U121 H2′–C123 H6 and A122 H2–G135 H1′ long-range NOEs are indicated in red. d, The A122 bulge forms a triple base interaction. Hydrogen bonds are shown in green, and the A122 H2–G135 H1′ distance is indicated by a solid black line. e, Strip plots of 13C edited 1H–1H planes from three-dimensional NOESY HMQC spectra of U5-PBS, showing interresidue NOE connectivities. Black, dashed lines show sequential inter-residue connectivities, while the orange lines represent long-range interactions. The strong G110 H8-to-H1′ intraresidue NOE is indicative of a syn glycosidic torsion angle. Residues in the PBS and NC binding site are labelled with blue and red, respectively. f, Lowest-energy AMBER structures of the (UCUGA111, UU146) internal loop, showing the flexibility of U107 due to lack of inter-residue NOEs. Alignment of residues 108–111 and 144–146 yields an r.m.s.d. of 0.8 ± 0.3 Å. g, Portions from three-dimensional NOESY-HMQC spectra collected for selectively labelled 13C,15N-U5-PBS. As evidence for the ribose-zipper motif, intense H1′–H1′ inter-residue connectivities are observed between U146 and C108, which are located on opposite strands. h, Portions from three-dimensional NOESY-HMQC spectra collected for selectively labelled 13C,15N-U5-PBS in complex with NC. Both the ribose and aromatic protons of U146 do not give rise to any inter-residue NOEs, indicating the lack of U146 interaction with neighbouring residues. An inset of the secondary structure of the bulge region is shown to visualize the availability of the released uracils. i, j, 1H–13C two-dimensional HMQC spectra collected with 0 (black) and 0.9 (red) equivalents of NC. Perturbation of G155, U156 signals towards the minor (indicated by an asterisk) conformation are shown by dashed lines. Blue asterisk indicates the emergence of new freed uridine resonances after NC addition. k, Specific perturbation of G100 is seen by selective loss of imino NOE to G101. l, A portion of two-dimensional NOESY spectra collected in D2O for a 1:1 Ψ-packaging signal–NC complex (black) and U5-PBS–NC complex (red). The complete match of the two data sets indicates that, similar to the Ψ–NC interaction19, the NC tails continue to exist in a random coil confirmation upon complex formation.
a, b, ITC data for NC interactions with the U5-PBS domain (monomeric form; see Supplementary Discussion 1) (a) and tRNAPro(b), along with their respective mutant RNAs (V1M = G110U; V2M = G130A; T1M = G9A; T2M = G35A,G36A,G37A; T3M was not made since G23 is part of a critical base triple). The Kd values are the averages of three independent experiments, n = 3. Continuous lines represent the fit for two- and three-site binding models for U5-PBS and tRNAPro, respectively. As expected, V1M is fit with a one-site binding model, while V1MV2M abolishes NC binding. Similarly, T1M and T2M are fit with two-site binding models, while T1MT2M is fit with a one-site binding model. Entropy values were calculated using T = 303 K. The net gain in entropy (green) and loss in enthalpy (red) are shown for site T2 in full-length tRNAPro in comparison with the isolated anticodon SLAC RNA. The favourable enthalpy resulting from zinc-finger interaction with the anticodon loop in tRNAPro (ΔH = −14.2 kcal mol−1) is offset by loss of enthalpy in RNA elements beyond the anticodon stem (loss of 9.8 kcal mol−1) and, consequently, a significant entropic compensation (gain of 11.5 kcal mol−1) is observed (see Supplementary Discussion 7). c, Titration of NC into a mixture of tRNAPro and U5-PBS. Lanes 1, 2, 3 and 4 correspond to 1, 2, 3 and 4 equivalents of NC. Addition of four equivalents of NC to a mixture of tRNAPro and U5-PBS led to a near complete annealing of the molecule. For this experiment, the U5-PBS dimeric construct was used because, for a functional assay, the entire 18-nucleotide primer binding site is required. NMR studies on this construct, however, showed that the construct is in equilibrium with the monomeric form. This experiment demonstrates that only a few NC molecules are required to yield a functional complex. d, Reverse transcription of heat-annealed versus NC-annealed U5-PBS–tRNAPro initiation complexes. The 10-nucleotide DNA product is obtained by reverse transcriptase terminating transcription after incorporating ddCTP at position 10 (and subsequent removal of the tRNA nucleotides by RNase treatment). e, ITC data for NC binding to tRNAPro T2M (AGGG37 is mutated to AAAA37). f, ITC data confirming that base modifications are not required for NC binding. ITC data (n = 3) were fit well with a one-site binding model. g, A packaging assay confirms that the mutations do not affect genome encapsidation (n = 6). As a positive control, the observed decrease for Ψ (C331G) control is similar to that previously observed37, and the non-template control (NTC) exhibits no viral RNA signal.
a, b, Two-dimensional 1H–1H NOESY spectra for the isolated anticodon stem loop (a) and full-length tRNAPro (b) constructs, with blue lines indicating inter- and intra-residue aromatic-to-H1′ NOE connectivities (see also Supplementary Discussion 4).
Extended Data Figure 6 Assignment of the acceptor–TΨC-stem loop construct confirms proper coaxial stacking in the context of the full-length tRNAPro tertiary structure.
a, b, Two-dimensional 1H–1H NOESY spectra for the isolated acceptor–TΨC-stem loop (a) and full-length tRNAPro (b) constructs, with black and red lines indicating inter- and intra-residue aromatic-to-H1′ NOE connectivities in the acceptor stem and TΨC-stem loop, respectively (see also Supplementary Discussion 4).
a, b, Spectra for the isolated D-stem loop (a) and full-length tRNAPro (b) constructs, with lines indicating inter- and intra-residue aromatic-to-H1′ NOE connectivities. The chemical shifts of residues in the D-stem loop are drastically altered in the context of the full-length tRNA due to the formation of multiple long-range interactions between the D-stem loop and other regions in the tertiary structure of tRNAPro. c, Extreme sensitivity of the tRNAPro elbow tertiary interaction to temperature. At higher temperature, the D-stem loop loses its long-range interaction with the TΨC-loop, and chemical shifts resemble those for the D-stem loop in the isolated form (see Supplementary Discussion 4). d, e, Sensitivity of the tRNAPro elbow tertiary interaction to magnesium divalent salt. The data show the downfield shift of the U54 base in the TΨC-loop and the characteristic signal for G16, G18 that arises as the D-loop becomes structured upon elbow interaction formation. In contrast, the bottom right panel shows the insensitivity of the isolated TΨC loop to divalent salts (see also Supplementary Discussion 4).
a, Imino resonances for full-length tRNAPro indicate proper tertiary structure formation. Portions of the 1H–15N two-dimensional HSQC spectra for U- (top) and G-labelled (centre) full-length tRNAPro constructs, with imino assignments indicated. A portion of the 1H–1H two-dimensional NOESY spectrum showing imino-to-imino NOEs is shown at the bottom. b, Two-dimensional NOESY of a GH sample of the T2M construct wherein only the guanosines were protonated and the other three nucleotides were deuterated. This mutant was chosen to unambiguously assign the G resonances from the D-loop and the variable loop by reducing the spectral complexity from the G-rich anticodon loop. c, Strips from fully protonated and G-protonated two-dimensional NOESY spectra showing direct evidence for the D-loop–TΨC interaction (see Supplementary Discussion 4). The left panel shows data collected at low temperature that allow us to confirm the long-range assignment because the A58 H1′ NOE spin diffuses to the aromatic proton of G19 via G18. d, Strips from fully protonated sample showing the NOE walk from the D-stem to the loop residue G15 that forms the critical Levitt base pair with C48. This arrangement leads to an unusual downfield shift of the C48 H1′ (see Supplementary Discussion 4).
a, The packing of U7 against the Tyr 28 side-chain protons leads to a downfield shift of the H5 and H1′ protons of U7. Intermolecular NOEs characteristic of the fourth G of an NNNG motif entering the hydrophobic pocket of the NC protein zinc finger are also observed for G9 of the GUUG9. An r(GUUG) construct essentially gives the same NOE pattern as the tRNAPro GUUG9 upon interacting with NC, and was used as a guide for assignments. This technique has been used previously for the genome-Ψ-packaging–NC complex. The tRNAPro T2M construct was used for assignments since it has no effect on site T1 binding but allows for unambiguous assignments; that is, it ensures that no NC is bound to the second site at 1:1 titration. Nevertheless, we have confirmed via HMQCs that identical site T1 binding chemical shifts are observed in the native and the T2M mutant. b, Portion of two-dimensional NOESY spectra collected with 0 (black) and 0.3 (red) NC equivalents. Selective perturbation of the helical walk between the 10th and 11th anti-PBS residues, −10C67 and −11A66, is shown. In contrast, the typical minor groove connectivity of the A69 H2 shows the preservation of adjacent intramolecular associations of the seventh (−7G68), eighth (−8A69) and ninth (−9G70) anti-PBS residues. c, A portion of two-dimensional NOESY spectrum showing H8/H1′ correlations for the selectively protonated T2M–GH tRNAPro sample. Data for the T2M construct are shown to demonstrate that the observed structural changes are due solely to NC binding to site T1 rather than site T2. Addition of only 0.1 NC equivalent results in immediate perturbation of specific signals (G6 and G9), confirming the location of the first NC binding site. d, e, Portion of two-dimensional NOESY spectra collected with 0 (black) and 0.3 (red) NC equivalents, showing the preservation of the stacking interaction between the D-stem and anticodon stem (e), whereas the walk between the acceptor stem and TΨC stem is disrupted (d). f, A portion of two-dimensional NOESY spectra collected in D2O for a 1:1 Ψ-packaging-signal–NC complex (black) and tRNAPro T2M–NC complex (red). The complete match of the two data sets indicates that, similar to the Ψ–NC interaction, the NC tails continue to exist in a random coil conformation upon complex formation19. g, Characteristic intermolecular NOEs from the G37 residue of the anticodon AGGG37 binding site to the NC zinc finger. The isolated anticodon (SL) construct essentially gives the same NOE pattern as the site T2 tRNAPro binding upon interacting with NC. However, this pattern is observed only upon titration of NC over 1:1 in the tRNAPro construct, demonstrating the sequential binding involved in NC-mediated remodelling. h, Characteristic intermolecular NOEs from the G23 residue from the UAUG23 binding site to the NC zinc finger. The tRNAPro T1MT2M construct NOE pattern was an exact match with that of the NC–r(UAUG)23 complex, explicitly confirming the third NC binding site, site T3. The delta proton of Tyr 28 proton of the NC protein displays an intermolecular NOE to the downfield-shifted H5 proton of U20, which indicates packing of RNA protons against the Tyr 28 side-chain protons. Furthermore, the presence of characteristic intermolecular NOEs between the H8 proton of G23 and the Trp 35 aromatic H5 and H6 protons indicates specific insertion of G23 into the hydrophobic pocket of the zinc knuckle domain of the NC protein. i, Structure of NC bound to tRNAPro T1MT2M.
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Miller, S., Yildiz, F., Lo, J. et al. A structure-based mechanism for tRNA and retroviral RNA remodelling during primer annealing. Nature 515, 591–595 (2014). https://doi.org/10.1038/nature13709
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