The work in this dissertation provides structural insight into picornavirus replication. The presumptive RNA cloverleaf at the start of the 5´-NCR of the picornavirus genome is an essential element in replication. Stem loop B (SLB) of the cloverleaf is a recognition site for the host PCBP, which initiates a switch from translation to replication. In chapter 2, the solution structure of HRV-14 SLB was determined using NMR spectroscopy. SLB adopts a predominantly A-form helical structure with five Watson-Crick base pairs and one wobble base pair, and is capped by an eight nucleotide loop. The wobble base pair introduces perturbations in the helical parameters, but does not appear to introduce flexibility. Due to the short length of the helix, major groove appears to be accessible. The accessible major groove allows for the access of protein interactions, potentially of PCBP, a interaction essential in replication. Unlike the helix, flexibility is seen throughout the loop and in the terminal nucleotides, with the pyrimidine-rich region, the apparent recognition site for the PCBP, being the most disordered region of the structure.
In chapter 3, using previously determined information from isolate solution structures of HRV-14 SLB and SLD, the solution structure of HRV-14 5ʹCL was determined using a combination of NMR and SAXS. Magnesium is known to stabilize RNA tertiary folding by shielding the negatively charged phosphates of the sugar phosphate backbone. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB and SLD into close contact, a geometry that creates an extensive
accessible major groove surface, and permits interaction between the proteins that target each stem loop. This work provides the first solution structure of the 5’CL in picornaviruses, a discovery necessary for a thorough understanding of picornavirus replication.
In Figure 23, 5’CL is modeled with poliovirus 3CD113 and the KH1 domain from
PCBP87. Future studies would include docking 3CD and PCBP protein to the 5’CL using
HADDOCK software114 to model the biomolecular complex. HADDOCK uses
experimental data, NMR distance constraints and RDC values, to determine the relative orientation of the each component in a complex. The model in Figure 23 can be compared to the HADDOCK docking model for further validation.
Since isolated SLB retained its conformation when incorporated in the 5’CL, the complex of isolated SLB and KH1-KH2 domain of PCBP can be determined using solution NMR and SAXS. The SLB-PCBP complex could then be used, along with the previously solved complex of SLD-3CD, to model the entire picornavirus replication complex in solution (5’CL-PCBP-3CD).
REFERENCES
[1] Pilipenko, E. V., Blinov, V. M., Romanova, L. I., Sinyakov, A. N., Maslova, S. V., and Agol, V. I. (1989) Conserved structural domains in the 5'-untranslated region of picornaviral genomes: an analysis of the segment controlling translation and neurovirulence, Virology 168, 201-209.
[2] Agol, V. I., Paul, A. V., and Wimmer, E. (1999) Paradoxes of the replication of picornaviral genomes, Virus Res 62, 129-147.
[3] Knowles, N., Hovi, T., King, A., and Stanway, G. (2010) Overview of taxonomy, The
picornaviruses. ASM Press, Washington, DC, 19-32.
[4] (2017) Examination of ancient Egyptian mummy with foot deformity from the new kingdom period, The Journal of Orthopaedics Tr auma Surgery and Related
Research 2, 29-31.
[5] Ehrenfeld, E., Domingo, E., and Roos, R. P. (2010) The Picornaviruses, American Society of Microbiology.
[6] Zaffran, M., McGovern, M., Hossaini, R., Martin, R., and Wenger, J. (2018) The polio endgame: securing a world free of all polioviruses, The Lancet 391, 11-13.
[7] Campos-Outcalt, D. (2018) CDC provides advice on recent hepatitis A outbreaks: Although rates of hepatitis A virus infection have steadily declined since 1995, recent spikes in community outbreaks compel a renewed effort in adult
immunization, In Journal of Family Practice, p 30+.
[8] Aretz, H. T., Billingham, M. E., Edwards, W. D., Factor, S. M., Fallon, J. T., Fenoglio, J. J., Jr., Olsen, E. G., and Schoen, F. J. (1987) Myocarditis. A histopathologic definition and classification, The American journal of cardiovascular pathology 1, 3-14.
[9] Messroghli, D. R., Pickardt, T., Fischer, M., Opgen-Rhein, B., Papakostas, K.,
Böcker, D., Jakob, A., Khalil, M., Mueller, G. C., Schmidt, F., Kaestner, M., Udink ten Cate, F. E. A., Wagner, R., Ruf, B., Kiski, D., Wiegand, G., Degener, F., Bauer, U. M. M., Friede, T., and Schubert, S. (2017) Toward evidence-based diagnosis of myocarditis in children and adolescents: Rationale, design, and first baseline data of MYKKE, a multicenter registry and study platform, American
Heart Journal 187, 133-144.
[10] Kitulwatte, I. D., Kim, P. J., and Pollanen, M. S. (2010) Sudden death related myocarditis: a study of 56 cases, Forensic science, medicine, and pathology 6, 13-19.
[11] Salguero, F. J., Sánchez-Martín, M. A., Díaz-San Segundo, F., de Avila, A., and Sevilla, N. (2005) Foot-and-mouth disease virus (FMDV) causes an acute disease that can be lethal for adult laboratory mice, Virology 332, 384-396. [12] Turner, R. B. (2007) Rhinovirus: More than Just a Common Cold Virus, Journal of
Infectious Diseases 195, 765-766.
[13] Jacobs, S. E., Lamson, D. M., St George, K., and Walsh, T. J. (2013) Human rhinoviruses, Clinical microbiology reviews 26, 135-162.
[14] Savolainen, C., Blomqvist, S., Mulders, M. N., and Hovi, T. (2002) Genetic
clustering of all 102 human rhinovirus prototype strains: serotype 87 is close to human enterovirus 70, The Journal of general virology 83, 333-340.
[15] Andrewes, C. H. (1950) Adventures among Viruses, New England Journal of
Medicine 242, 235-240.
[16] Stanway, G., Hughes, P. J., Mountford, R. C., Minor, P. D., and Almond, J. W. (1984) The complete nucleotide sequence of a common cold virus: human rhinovirus 14, Nucleic acids research 12, 7859-7875.
[17] Erickson, J. W., Frankenberger, E. A., Rossmann, M. G., Fout, G. S., Medappa, K. C., and Rueckert, R. R. (1983) Crystallization of a common cold virus, human rhinovirus 14: "isomorphism" with poliovirus crystals, Proceedings of the National
Academy of Sciences of the United States of America 80, 931-934.
[18] Rohll, J. B., Percy, N., Ley, R., Evans, D. J., Almond, J. W., and Barclay, W. S. (1994) The 5'-untranslated regions of picornavirus RNAs contain independent functional domains essential for RNA replication and translation, Journal of
virology 68, 4384-4391.
[19] Herold, J., and Andino, R. (2001) Poliovirus RNA replication requires genome circularization through a protein-protein bridge, Molecular cell 7, 581-591. [20] Dreher, T. W. (1999) FUNCTIONS OF THE 3′-UNTRANSLATED REGIONS OF
POSITIVE STRAND RNA VIRAL GENOMES, Annual Review of Phytopathology
37, 151-174.
[21] Palmenberg, A. C., and Gern, J. E. (2015) Classification and evolution of human rhinoviruses, Methods in molecular biology (Clifton, N.J.) 1221, 1-10.
[22] Rieder, E., Xiang, W., Paul, A., and Wimmer, E. (2003) Analysis of the cloverleaf element in a human rhinovirus type 14/poliovirus chimera: correlation of
subdomain D structure, ternary protein complex formation and virus replication,
The Journal of general virology 84, 2203-2216.
[23] Paul, A. V., van Boom, J. H., Filippov, D., and Wimmer, E. (1998) Protein-primed RNA synthesis by purified poliovirus RNA polymerase, Nature 393, 280-284. [24] Parks, G. D., Baker, J. C., and Palmenberg, A. C. (1989) Proteolytic cleavage of
encephalomyocarditis virus capsid region substrates by precursors to the 3C enzyme, Journal of virology 63, 1054-1058.
[25] Gamarnik, A. V., and Andino, R. (1998) Switch from translation to RNA replication in a positive-stranded RNA virus, Genes & Development 12, 2293-2304.
[26] Walter, B. L., Parsley, T. B., Ehrenfeld, E., and Semler, B. L. (2002) Distinct Poly(rC) Binding Protein KH Domain Determinants for Poliovirus Translation Initiation and Viral RNA Replication, Journal of virology 76, 12008-12022.
[27] Spear, A., Sharma, N., and Flanegan, J. B. (2008) Protein–RNA tethering: The role of poly(C) binding protein 2 in poliovirus RNA replication, Virology 374, 280-291. [28] Arnold, J. J., Ghosh, S. K., and Cameron, C. E. (1999) Poliovirus RNA-dependent
RNA polymerase (3D(pol)). Divalent cation modulation of primer, template, and nucleotide selection, The Journal of biological chemistry 274, 37060-37069. [29] Paul, A. V., Rieder, E., Kim, D. W., van Boom, J. H., and Wimmer, E. (2000)
Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg, Journal of virology 74, 10359-10370. [30] Headey, S. J., Huang, H., Claridge, J. K., Soares, G. A., Dutta, K., Schwalbe, M.,
Yang, D., and Pascal, S. M. (2007) NMR structure of stem–loop D from human rhinovirus-14, RNA (New York, N.Y.) 13, 351-360.
[31] Ohlenschlager, O., Wohnert, J., Bucci, E., Seitz, S., Hafner, S., Ramachandran, R., Zell, R., and Gorlach, M. (2004) The structure of the stemloop D subdomain of coxsackievirus B3 cloverleaf RNA and its interaction with the proteinase 3C,
Structure (London, England : 1993) 12, 237-248.
[32] Du, Z., Yu, J., Ulyanov, N. B., Andino, R., and James, T. L. (2004) Solution
structure of a consensus stem-loop D RNA domain that plays important roles in regulating translation and replication in enteroviruses and rhinoviruses,
Biochemistry 43, 11959-11972.
[33] Andino, R., Rieckhof, G. E., Achacoso, P. L., and Baltimore, D. (1993) Poliovirus RNA synthesis utilizes an RNP complex formed around the 5'-end of viral RNA,
Embo j 12, 3587-3598.
[34] Andino, R., Rieckhof, G. E., and Baltimore, D. (1990) A functional ribonucleoprotein complex forms around the 5′ end of poliovirus RNA, Cell 63, 369-380.
[35] Parisien, M., and Major, F. (2008) The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data, Nature 452, 51-55.
[36] Claridge, J. K., Headey, S. J., Chow, J. Y., Schwalbe, M., Edwards, P. J., Jeffries, C. M., Venugopal, H., Trewhella, J., and Pascal, S. M. (2009) A picornaviral loop- to-loop replication complex, J Struct Biol 166, 251-262.
[37] Williams, B., 2nd, Zhao, B., Tandon, A., Ding, F., Weeks, K. M., Zhang, Q., and Dokholyan, N. V. (2017) Structure modeling of RNA using sparse NMR constraints, Nucleic acids research 45, 12638-12647.
[38] Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., and Bourne, P. E. (2000) The Protein Data Bank, Nucleic acids
research 28, 235-242.
[39] Marino, J. P., Schwalbe, H., and Griesinger, C. (1999) J-Coupling Restraints in RNA Structure Determination, Accounts of Chemical Research 32, 614-623. [40] Rich, A. (1998) The rise of single-molecule DNA biochemistry, Proceedings of the
National Academy of Sciences of the United States of America 95, 13999-14000.
[41] Clore, G. M., Starich, M. R., Bewley, C. A., Cai, M., and Kuszewski, J. (1999) Impact of Residual Dipolar Couplings on the Accuracy of NMR Structures
Determined from a Minimal Number of NOE Restraints, Journal of the American
Chemical Society 121, 6513-6514.
[42] Cornilescu, G., Didychuk, A. L., Rodgers, M. L., Michael, L. A., Burke, J. E.,
Montemayor, E. J., Hoskins, A. A., and Butcher, S. E. (2016) Structural Analysis of Multi-Helical RNAs by NMR-SAXS/WAXS: Application to the U4/U6 di-snRNA,
J Mol Biol 428, 777-789.
[43] Burke, J. E., Sashital, D. G., Zuo, X., Wang, Y. X., and Butcher, S. E. (2012) Structure of the yeast U2/U6 snRNA complex, RNA (New York, N.Y.) 18, 673- 683.
[44] Grishaev, A., Ying, J., Canny, M. D., Pardi, A., and Bax, A. (2008) Solution
structure of tRNAVal from refinement of homology model against residual dipolar coupling and SAXS data, Journal of biomolecular NMR 42, 99-109.
[45] Jacques, D. A., and Trewhella, J. (2010) Small-angle scattering for structural biology--expanding the frontier while avoiding the pitfalls, Protein science : a
[46] Woenckhaus, J., Köhling, R., Thiyagarajan, P., Littrell, K. C., Seifert, S., Royer, C. A., and Winter, R. (2001) Pressure-Jump Small-Angle X-Ray Scattering Detected Kinetics of Staphylococcal Nuclease Folding, Biophysical Journal 80, 1518-1523. [47] Vestergaard, B., Sanyal, S., Roessle, M., Mora, L., Buckingham, R. H., Kastrup, J.
S., Gajhede, M., Svergun, D. I., and Ehrenberg, M. (2005) The SAXS solution structure of RF1 differs from its crystal structure and is similar to its ribosome bound cryo-EM structure, Molecular cell 20, 929-938.
[48] Goodfellow, I., Chaudhry, Y., Richardson, A., Meredith, J., Almond, J. W., Barclay, W., and Evans, D. J. (2000) Identification of a cis-acting replication element within the poliovirus coding region, Journal of virology 74, 4590-4600.
[49] Jacobson, S. J., Konings, D. A., and Sarnow, P. (1993) Biochemical and genetic evidence for a pseudoknot structure at the 3' terminus of the poliovirus RNA genome and its role in viral RNA amplification, Journal of virology 67, 2961-2971. [50] Le, S.-Y., and Zuker, M. (1990) Common structures of the 5′ non-coding RNA in
enteroviruses and rhinoviruses: Thermodynamical stability and statistical significance, Journal of Molecular Biology 216, 729-741.
[51] Rivera, V. M., Welsh, J. D., and Maizel Jr, J. V. (1988) Comparative sequence analysis of the 5′ noncoding region of the enteroviruses and rhinoviruses,
Virology 165, 42-50.
[52] Gamarnik, A. V., and Andino, R. (1997) Two functional complexes formed by KH domain containing proteins with the 5' noncoding region of poliovirus RNA, RNA
(New York, N.Y.) 3, 882-892.
[53] Parsley, T. B., Towner, J. S., Blyn, L. B., Ehrenfeld, E., and Semler, B. L. (1997) Poly (rC) binding protein 2 forms a ternary complex with the 5'-terminal
sequences of poliovirus RNA and the viral 3CD proteinase, RNA (New York,
N.Y.) 3, 1124-1134.
[54] Barton, D. J., O'Donnell, B. J., and Flanegan, J. B. (2001) 5' cloverleaf in poliovirus RNA is a cis-acting replication element required for negative-strand synthesis,
Embo j 20, 1439-1448.
[55] Blyn, L. B., Swiderek, K. M., Richards, O., Stahl, D. C., Semler, B. L., and Ehrenfeld, E. (1996) Poly(rC) binding protein 2 binds to stem-loop IV of the poliovirus RNA 5' noncoding region: identification by automated liquid chromatography-tandem mass spectrometry, Proceedings of the National
Academy of Sciences of the United States of America 93, 11115-11120.
[56] Blyn, L. B., Towner, J. S., Semler, B. L., and Ehrenfeld, E. (1997) Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA, Journal of virology 71, 6243-6246.
[57] Back, S. H., Kim, Y. K., Kim, W. J., Cho, S., Oh, H. R., Kim, J. E., and Jang, S. K. (2002) Translation of polioviral mRNA is inhibited by cleavage of polypyrimidine tract-binding proteins executed by polioviral 3C(pro), Journal of virology 76, 2529-2542.
[58] Perera, R., Daijogo, S., Walter, B. L., Nguyen, J. H., and Semler, B. L. (2007) Cellular protein modification by poliovirus: the two faces of poly(rC)-binding protein, Journal of virology 81, 8919-8932.
[60] Lavery, R., Moakher, M., Maddocks, J. H., Petkeviciute, D., and Zakrzewska, K. (2009) Conformational analysis of nucleic acids revisited: Curves+, Nucleic acids
research 37, 5917-5929.
[61] Baba, S., Kajikawa, M., Okada, N., and Kawai, G. (2004) Solution structure of an RNA stem–loop derived from the 3′ conserved region of eel LINE UnaL2, RNA
(New York, N.Y.) 10, 1380-1387.
[62] Schwieters, C. D., Kuszewski, J. J., Tjandra, N., and Clore, G. M. (2003) The Xplor- NIH NMR molecular structure determination package, J Magn Reson 160, 65-73. [63] Eichhorn, C. D., Feng, J., Suddala, K. C., Walter, N. G., Brooks, C. L., and Al-
Hashimi, H. M. (2012) Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch,
Nucleic acids research 40, 1345-1355.
[64] Popovic, M., and Greenbaum, N. L. (2014) Role of helical constraints of the EBS1- IBS1 duplex of a group II intron on demarcation of the 5' splice site, RNA (New
York, N.Y.) 20, 24-35.
[65] Kishore, A. I., Mayer, M. R., and Prestegard, J. H. (2005) Partial 13C isotopic enrichment of nucleoside monophosphates: useful reporters for NMR structural studies, Nucleic acids research 33, e164.
[66] Shajani, Z., Drobny, G., and Varani, G. (2007) Binding of U1A protein changes RNA dynamics as observed by 13C NMR relaxation studies, Biochemistry 46, 5875-5883.
[67] Zhang, Q., Sun, X., Watt, E. D., and Al-Hashimi, H. M. (2006) Resolving the Motional Modes That Code for RNA Adaptation, Science (New York, N.Y.) 311, 653-656.
[68] Eichhorn, C. D., and Al-Hashimi, H. M. (2014) Structural dynamics of a single- stranded RNA-helix junction using NMR, RNA (New York, N.Y.) 20, 782-791. [69] Getz, M., Sun, X., Casiano-Negroni, A., Zhang, Q., and Al-Hashimi, H. M. (2007)
NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings, Biopolymers 86, 384-402.
[70] Tolman, J. R., Flanagan, J. M., Kennedy, M. A., and Prestegard, J. H. (1997) NMR evidence for slow collective motions in cyanometmyoglobin, Nat Struct Mol Biol
4, 292-297.
[71] Tolman, J. R., and Ruan, K. (2006) NMR Residual Dipolar Couplings as Probes of Biomolecular Dynamics, Chemical Reviews 106, 1720-1736.
[72] Kailasam, S., Bhattacharyya, D., and Bansal, M. (2014) Sequence dependent variations in RNA duplex are related to non-canonical hydrogen bond interactions in dinucleotide steps, BMC Res Notes 7, 83.
[73] Pingali, P. K., Halder, S., Mukherjee, D., Basu, S., Banerjee, R., Choudhury, D., and Bhattacharyya, D. (2014) Analysis of stacking overlap in nucleic acid structures: algorithm and application, J Comput Aided Mol Des 28, 851-867. [74] Hermann, T., and Westhof, E. (1999) Non-Watson-Crick base pairs in RNA-protein
recognition, Chem Biol 6, R335-343.
[75] Lu, X. J., and Olson, W. K. (2003) 3DNA: a software package for the analysis, rebuilding and visualization of three‐dimensional nucleic acid structures, Nucleic
[76] Ananth, P., Goldsmith, G., and Yathindra, N. (2013) An innate twist between Crick's wobble and Watson-Crick base pairs, RNA (New York, N.Y.) 19, 1038-1053. [77] Du, Z., Yu, J., Andino, R., and James, T. L. (2003) Extending the family of UNCG-
like tetraloop motifs: NMR structure of a CACG tetraloop from coxsackievirus B3,
Biochemistry 42, 4373-4383.
[78] Joli, F., Bouchemal, N., Laigle, A., Hartmann, B., and Hantz, E. (2006) Solution structure of a purine rich hexaloop hairpin belonging to PGY/MDR1 mRNA and targeted by antisense oligonucleotides, Nucleic acids research 34, 5740-5751. [79] Mueller, U., Schübel, H., Sprinzl, M., and Heinemann, U. (1999) Crystal structure of
acceptor stem of tRNA(Ala) from Escherichia coli shows unique G.U wobble base pair at 1.16 A resolution, RNA (New York, N.Y.) 5, 670-677.
[80] Trikha, J., Filman, D. J., and Hogle, J. M. (1999) Crystal structure of a 14 bp RNA duplex with non-symmetrical tandem G·U wobble base pairs, Nucleic acids
research 27, 1728-1739.
[81] Varani, G., and McClain, W. H. (2000) The G x U wobble base pair. A fundamental building block of RNA structure crucial to RNA function in diverse biological systems, EMBO Rep 1, 18-23.
[82] El Hassan, M. A., and Calladine, C. R. (1998) Two distinct modes of protein- induced bending in DNA, J Mol Biol 282, 331-343.
[83] Huang, H., Alexandrov, A., Chen, X., Barnes, T. W., 3rd, Zhang, H., Dutta, K., and Pascal, S. M. (2001) Structure of an RNA hairpin from HRV-14, Biochemistry 40, 8055-8064.
[84] Chase, A. J., Daijogo, S., and Semler, B. L. (2014) Inhibition of poliovirus-induced cleavage of cellular protein PCBP2 reduces the levels of viral RNA replication,
Journal of virology 88, 3192-3201.
[85] Silvera, D., Gamarnik, A. V., and Andino, R. (1999) The N-terminal K Homology Domain of the Poly(rC)-binding Protein Is a Major Determinant for Binding to the Poliovirus 5′-Untranslated Region and Acts as an Inhibitor of Viral Translation,
Journal of Biological Chemistry 274, 38163-38170.
[86] Du, Z., Lee, J. K., Fenn, S., Tjhen, R., Stroud, R. M., and James, T. L. (2007) X-ray crystallographic and NMR studies of protein–protein and protein–nucleic acid interactions involving the KH domains from human poly(C)-binding protein-2,
RNA (New York, N.Y.) 13, 1043-1051.
[87] Du, Z., Lee, J. K., Tjhen, R., Li, S., Pan, H., Stroud, R. M., and James, T. L. (2005) Crystal Structure of the First KH Domain of Human Poly(C)-binding Protein-2 in Complex with a C-rich Strand of Human Telomeric DNA at 1.7 Å, Journal of
Biological Chemistry 280, 38823-38830.
[88] Sharma, N., Ogram, S. A., Morasco, B. J., Spear, A., Chapman, N. M., and Flanegan, J. B. (2009) Functional role of the 5' terminal cloverleaf in Coxsackievirus RNA replication, Virology 393, 238-249.
[89] Greenberg, S. B. (2003) Respiratory consequences of rhinovirus infection, Archives
of Internal Medicine 163, 278-284.
[90] Goodfellow, I. G., Kerrigan, D., and Evans, D. J. (2003) Structure and function analysis of the poliovirus cis-acting replication element (CRE), RNA (New York,
[91] Ying, J., Wang, J., Grishaev, A., Yu, P., Wang, Y.-X., and Bax, A. (2011)
Measurement of (1)H-(15)N and (1)H-(13)C residual dipolar couplings in nucleic acids from TROSY intensities, Journal of biomolecular NMR 51, 89-103.
[92] Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., and Bax, A. (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes,
Journal of biomolecular NMR 6, 277-293.
[93] Norris, M., Fetler, B., Marchant, J., and Johnson, B. A. (2016) NMRFx Processor: a cross-platform NMR data processing program, Journal of biomolecular NMR 65, 205-216.
[94] Petoukhov, M. V., Franke, D., Shkumatov, A. V., Tria, G., Kikhney, A. G., Gajda, M., Gorba, C., Mertens, H. D., Konarev, P. V., and Svergun, D. I. (2012) New developments in the ATSAS program package for small-angle scattering data analysis, J Appl Crystallogr 45, 342-350.
[95] Svergun, D. I. (1992) Determination of the Regularization Parameter in Indirect-
Transform Methods Using Perceptual Criteria, Vol. 25.
[96] Franke, D., and Svergun, D. I. (2009) DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering, J Appl Crystallogr 42, 342-346.
[97] Svergun, D. I., Barberato, C., and Koch, M. (1995) CRYSOL– a Program to
Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates, Vol. 28.
[98] Kozin, M. B., Svergun, D. I., and Embl, B. (2001) Automated matching of high- and
low-resolution structural models, Vol. 34.
[99] Rambo, R. P., and Tainer, J. A. (2013) Accurate assessment of mass, models and resolution by small-angle scattering, Nature 496, 477-481.
[100] Warden, M. S., Tonelli, M., Cornilescu, G., Liu, D., Hopersberger, L. J., Ponniah, K., and Pascal, S. M. (2017) Structure of RNA Stem Loop B from the
Picornavirus Replication Platform, Biochemistry 56, 2549-2557.
[101] Popenda, M., Szachniuk, M., Antczak, M., Purzycka, K. J., Lukasiak, P., Bartol, N., Blazewicz, J., and Adamiak, R. W. (2012) Automated 3D structure
composition for large RNAs, Nucleic acids research 40, e112-e112.
[102] Zweckstetter, M. (2008) NMR: prediction of molecular alignment from structure using the PALES software, Nat Protoc 3, 679-690.
[103] Kikhney, A. G., and Svergun, D. I. (2015) A practical guide to small angle X-ray scattering (SAXS) of flexible and intrinsically disordered proteins, FEBS letters
589, 2570-2577.
[104] Laing, C., and Schlick, T. (2009) Analysis of four-way junctions in RNA structures,
J Mol Biol 390, 547-559.
[105] Gonzalez, R. L., and Tinoco, I. (2001) Identification and characterization of metal ion binding sites in RNA, Methods Enzymol 338, 421-443.
[106] Woodson, S. A. (2005) Metal ions and RNA folding: a highly charged topic with a dynamic future, Current Opinion in Chemical Biology 9, 104-109.
[107] Tinoco, I., and Bustamante, C. (1999) How RNA folds, Journal of Molecular
Biology 293, 271-281.
[108] Mertens, H. D. T., and Svergun, D. I. (2017) Combining NMR and small angle X- ray scattering for the study of biomolecular structure and dynamics, Archives of
[109] Correll, C. C., Freeborn, B., Moore, P. B., and Steitz, T. A. (1997) Metals, Motifs, and Recognition in the Crystal Structure of a 5S rRNA Domain, Cell 91, 705-712. [110] Tanaka, Y., Fujii, S., Hiroaki, H., Sakata, T., Tanaka, T., Uesugi, S., Tomita, K.,
and Kyogoku, Y. (1999) A'-form RNA double helix in the single crystal structure of r(UGAGCUUCGGCUC), Nucleic acids research 27, 949-955.
[111] Simon, B., Masiewicz, P., Ephrussi, A., and Carlomagno, T. (2015) The structure of the SOLE element of oskar mRNA, RNA (New York, N.Y.) 21, 1444-1453. [112] Battiste, J. L., Mao, H., Rao, N. S., Tan, R., Muhandiram, D. R., Kay, L. E.,
Frankel, A. D., and Williamson, J. R. (1996) Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA complex, Science (New York,
N.Y.) 273, 1547-1551.
[113] Marcotte, L. L., Wass, A. B., Gohara, D. W., Pathak, H. B., Arnold, J. J., Filman, D. J., Cameron, C. E., and Hogle, J. M. (2007) Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase, Journal of virology 81, 3583-3596.
[114] Dominguez, C., Boelens, R., and Bonvin, A. M. J. J. (2003) HADDOCK: A Protein−Protein Docking Approach Based on Biochemical or Biophysical Information, Journal of the American Chemical Society 125, 1731-1737.
APPENDIX A