Abstract
We examined how static and dynamic deviations from the idealized A-form helix propagate into errors in the principal order tensor parameters determined using residual dipolar couplings (rdcs). A 20-ns molecular dynamics (MD) simulation of the HIV-1 transactivation response element (TAR) RNA together with a survey of spin relaxation studies of RNA dynamics reveals that pico-to-nanosecond local motions in non-terminal Watson–Crick base-pairs will uniformly attenuate base and sugar one bond rdcs by ∼7%. Gaussian distributions were generated for base and sugar torsion angles through statistical comparison of 40 RNA X-ray structures solved to <3.0 Å resolution. For a typical number (≥11) of one bond C–H base and sugar rdcs, these structural deviations together with rdc uncertainty (1.5 Hz) lead to average errors in the magnitude and orientation of the principal axis of order that are <9% and <4°, respectively. The errors decrease to <5% and <4° for ≥17 rdcs. A protocol that allows for estimation of error in A-form order tensors due to both angular deviations and rdc uncertainty (Aform-RDC) is validated using theoretical simulations and used to analyze rdcs measured previously in TAR in the free state and bound to four distinct ligands. Results confirm earlier findings that the two TAR helices undergo large changes in both their mean relative orientation and dynamics upon binding to different targets.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aboul-ela F., Karn J., Varani G. (1995) J. Mol. Biol. 253:313–332
Aboul-ela F., Karn J., Varani G. (1996) Nucleic Acids Res. 24:3974–3981
Al-Hashimi H.M. (2005) Chembiochem 6:1506–1519
Al-Hashimi H.M., Gorin A., Majumdar A., Gosser Y., Patel D.J. (2002a) J. Mol. Biol. 318:637–649
Al-Hashimi H.M., Gosser Y., Gorin A., Hu W., Majumdar A., Patel D.J. (2002b) J. Mol. Biol. 315:95–102
Al-Hashimi H.M., Pitt S.W., Majumdar A., Xu W., Patel D.J. (2003) J. Mol. Biol. 329:867–873
Berman H.M., Olson W.K., Beveridge D.L., Westbrook J., Gelbin A., Demeny T., Hsieh S.H., Srinivasan A.R., Schneider B. (1992) Biophys. J. 63:751–759
Boisbouvier J., Bryce D.L., O’Neil-Cabello E., Nikonowicz E.P., Bax A. (2004) J. Biomol. NMR 30:287–301
Bondensgaard K., Mollova E.T., Pardi A. (2002) Biochemistry 41:11532–11542
Brooks C.L., Karplus M. (1983) J. Chem. Phys. 79:6312–6325
Bruschweiler R. (2003) Curr Opin Struct Biol 13:175–183
Bryce D.L., Boisbouvier J., Bax A. (2004) J. Am. Chem. Soc. 126:10820–10821
Cornell W.D., Cieplak P., Bayly C.I., Gould I.R., Merz K.M., Ferguson D.M., Spellmeyer D.C., Fox T., Caldwell J.W., Kollman P.A. (1995) J. Am. Chem. Soc. 117:5179–5197
Dickerson, R.E. (1988) Nucleic Acids Res, 17(5) 1797–1803
Du Z., Lind K.E., James T.L. (2002) Chem. Biol. 9:707–712
Duchardt E., Schwalbe H. (2005) J. Biomol. NMR 32:295–308
Faber C., Sticht H., Schweimer K., Rosch P. (2000) J. Biol. Chem. 275:20660–20666
Gelbin A., Schneider B., Clowney L., Hsieh S.H., Olson W.K., Berman H.M. (1996) J. Am. Chem. Soc. 118:519–529
Hansen A.L., Al-Hashimi H.M. (2006) J. Magn. Reson. 179:299–307
Hoover W.G. (1985) Phys. Rev. A 31:1695–1697
Ippolito J.A., Steitz T.A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95:9819–9824
Jaroniec C.P., Boisbouvier J., Tworowska I., Nikonowicz E.P., Bax A. (2005) J. Biomol. NMR 31:231–241
Jorgensen W.L., Chandrasekhar J., Madura J.D., Impey R.W., Klein M.L. (1983) J. Chem. Phys. 79:926–935
Klein D.J., Schmeing T.M., Moore P.B., Steitz T.A. (2001) Embo J 20:4214–4221
Leulliot N., Varani G. (2001) Biochemistry 40:7947–7956
Lilley D.M. (2004) Methods Mol. Biol. 252:77–108
Lipari G., Szabo A. (1982) J. Am. Chem. Soc. 104:4546–4559
Losonczi J.A., Andrec M., Fischer M.W.F., Prestegard J.H. (1999) J. Magn. Reson. 138:334–342
Lu X.J., Olson W.K. (2003) Nucleic Acids Res. 31:5108–5121
MacKerell A.D., Banavali N., Foloppe N. (2000) Biopolymers 56:257–265
McCallum S.A., Pardi A. (2003) J. Mol. Biol. 326:1037–1050
Mollova E.T., Hansen M.R., Pardi A. (2000) J. Am. Chem. Soc. 122:11561–11562
Moore P.B. (1999) Annu. Rev. Biochem. 68:287–300
Neidle S. (1999) Oxford Handbook of Nucleic Acid Structure. Oxford University Press, New York
Nose S. (1984) J. Chem. Phys. 81:511–519
O’Neil-Cabello E., Bryce D.L., Nikonowicz E.P., Bax A. (2004) J. Am. Chem. Soc. 126:66–67
Olson W.K., Bansal M., Burley S.K., Dickerson R.E., Gerstein M., Harvey S.C., Heinemann U., Lu X., Neidle S., Sakked Z., Sklenar H., Suzuki M., Tung C., Weshof E., Wolberger C., Berman H.M. (2001) J. Mol. Biol. 313:229–237
Pitt S.W., Majumdar A., Serganov A., Patel D.J., Al-Hashimi H.M. (2004) J. Mol. Biol. 338:7–16
Pitt S.W., Zhang Q., Patel D.J., Al-Hashimi H.M. (2005) Angew. Chem. Int. Ed. Engl. 44:3412–3415
Prestegard J.H., Al-Hashimi H.M., Tolman J.R. (2000) Q. Rev. Biophys. 33:371–424
Puglisi J.D., Tan R., Calnan B.J., Frankel A.D., Williamson J.R. (1992) Science 257:76–80
Ramirez B.E., Bax A. (1998) J. Am. Chem. Soc. 120:9106–9107
Reiter N.J., Blad H., Abildgaard F., Butcher S.E. (2004) Biochemistry 43:13739–13747
Saupe A. (1968) Angew. Chem., Int. Ed. Engl. 7:97–112
Shajani Z., Varani G. (2005) J. Mol. Biol. 349:699–715
Showalter S.A., Baker N.A., Tang C.G., Hall K. (2005) J. Biomol. NMR 32:179–193
Sibille N., Pardi A., Simorre J.P., Blackledge M. (2001) J. Am. Chem. Soc. 123:12135–12146
Sun G., Voigt J.H., Filippov I.V., Marquez V.E., Nicklaus M.C. (2004) J. Chem. Inf. Comput. Sci. 44:1752–1762
Tjandra N., Bax A. (1997) Science 278:1111–1114
Tolman J.R., Al-Hashimi H.M., Kay L.E., Prestegard J.H. (2001) J. Am. Chem. Soc. 123:1416–1424
Tolman J.R., Flanagan J.M., Kennedy M.A., Prestegard J.H. (1995) Proc. Natl. Acad. Sci. U. S. A. 92:9279–9283
Tolman J.R., Flanagan J.M., Kennedy M.A., Prestegard J.H. (1997) Nat. Struct. Biol. 4:292–297
Trantirek L., Urbasek M., Stefl R., Feigon J., Sklenar V. (2000) J. Am. Chem. Soc. 122:10454–10455
Vallurupalli P., Kay L.E. (2005) J. Am. Chem. Soc. 127:6893–6901
van Buuren B.N., Schleucher J., Wittmann V., Griesinger C., Schwalbe H., Wijmenga S.S. (2004) Angew. Chem. Int. Ed. Engl. 43:187–192
Warren J.J., Moore P.B. (2001) J. Biomol. NMR 20:311–323
Zhang Q., Sun X., Watt E.D., Al-Hashimi H.M. (2006) Science 311:653–656
Zhang Q., Throolin R., Pitt S.W., Serganov A., Al-Hashimi H.M. (2003) J. Am. Chem. Soc 125:10530–10531
Zweckstetter M. (2003) J. Biomol. NMR 27:41–56
Zweckstetter M., Bax A. (2002) J. Biomol. NMR 23:127–137
Acknowledgements
We thank members of the Al-Hashimi lab especially Alex Hansen and Qi Zhang for insightful comments. The authors gratefully acknowledge the Michigan Economic Development Cooperation and the Michigan Technology Tri-Corridor for the support of the purchase 600 MHz spectrometer. CM acknowledges financial support from an NIH sponsored Molecular Biophysics Training Grant. IA acknowledges support from the NSF CAREER Award. HMA acknowledges support from NIH grant RO1 AI066975-01. All programs implemented in this work are available from hashimi@umich.edu.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Musselman, C., Pitt, S.W., Gulati, K. et al. Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings. J Biomol NMR 36, 235–249 (2006). https://doi.org/10.1007/s10858-006-9087-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10858-006-9087-9