help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tang, Y.
Right arrow Articles by Nilsson, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tang, Y.
Right arrow Articles by Nilsson, L.

Biophys J, September 1999, p. 1284-1305, Vol. 77, No. 3

Molecular Dynamics Simulations of the Complex between Human U1A Protein and Hairpin II of U1 Small Nuclear RNA and of Free RNA in Solution

Yun Tang and Lennart Nilsson

Center for Structural Biochemistry, Department of Bioscience at Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden

RNA-protein interactions are essential to a wide range of biological processes. In this paper, a 0.6-ns molecular dynamics simulation of the sequence-specific interaction of human U1A protein with hairpin II of U1 snRNA in solution, together with a 1.2-ns simulation of the free RNA hairpin, is reported. Compared to the findings in the x-ray structure of the complex, most of the interactions remained stable. The nucleotide U8, one of the seven conserved nucleotides AUUGCAC in the loop region, was unusually flexible during the simulation, leading to a loss of direct contacts with the protein, in contrast to the situation in the x-ray structure. Instead the sugar-phosphate backbone of nucleotide C15 was found to form several interactions with the protein. Compared to the NMR structure of U1A protein complexed with the 3'-untranslated region of its own pre-mRNA, the protein core kept the same conformation, and in the two RNA molecules the conserved AUUGCAC of the loop and the closest CG base pair were located in very similar positions and orientations, and underwent very similar interactions with the protein. Therefore, a common sequence-specific interaction mechanism was suggested for the two RNA substrates to bind to the U1A protein. Conformational analysis of the RNA hairpin showed that the conformational changes of the RNA primarily occurred in the loop region, which is just involved in the sites of binding to the protein and in agreement with experimental observation. Both the loop and stem of the RNA became more ordered upon binding to the protein. It was also demonstrated that the molecular dynamics method could be successfully used to simulate the dynamical behavior of a large RNA-protein complex in aqueous solution, thus opening a path for the exploration of the complex biological processes involving RNA at a molecular level.

Biophys J, September 1999, p. 1284-1305, Vol. 77, No. 3
© 1999 by the Biophysical Society   0006-3495/99/09/1284/22  $2.00


This article has been cited by other articles:


Home page
 Biophys. JHome page
E. Olkhova, E. Padan, and H. Michel
The Influence of Protonation States on the Dynamics of the NhaA Antiporter from Escherichia coli
Biophys. J., June 1, 2007; 92(11): 3784 - 3791.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. J. Law, M. E. Linde, E. J. Chambers, C. Oubridge, P. S. Katsamba, L. Nilsson, I. S. Haworth, and I. A. Laird-Offringa
The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA
Nucleic Acids Res., January 10, 2006; 34(1): 275 - 285.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
S. A. Showalter and K. B. Hall
Correlated Motions in the U1 snRNA Stem/Loop 2:U1A RBD1 Complex
Biophys. J., September 1, 2005; 89(3): 2046 - 2058.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. J. Law, E. J. Chambers, P. S. Katsamba, I. S. Haworth, and I. A. Laird-Offringa
Kinetic analysis of the role of the tyrosine 13, phenylalanine 56 and glutamine 54 network in the U1A/U1 hairpin II interaction
Nucleic Acids Res., May 24, 2005; 33(9): 2917 - 2928.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
E. Olkhova, M. C. Hutter, M. A. Lill, V. Helms, and H. Michel
Dynamic Water Networks in Cytochrome c Oxidase from Paracoccus denitrificans Investigated by Molecular Dynamics Simulations
Biophys. J., April 1, 2004; 86(4): 1873 - 1889.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
T. Castrignano, G. Chillemi, G. Varani, and A. Desideri
Molecular Dynamics Simulation of the RNA Complex of a Double-Stranded RNA-Binding Domain Reveals Dynamic Features of the Intermolecular Interface and Its Hydration
Biophys. J., December 1, 2002; 83(6): 3542 - 3552.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. S. Katsamba, M. Bayramyan, I. S. Haworth, D. G. Myszka, and I. A. Laird-Offringa
Complex role of the beta 2-beta 3 Loop in the Interaction of U1A with U1 Hairpin II RNA
J. Biol. Chem., August 30, 2002; 277(36): 33267 - 33274.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
R. Nifosi, C. M. Reyes, and P. A. Kollman
Molecular dynamics studies of the HIV-1 TAR and its complex with argininamide
Nucleic Acids Res., December 15, 2000; 28(24): 4944 - 4955.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. S. Katsamba, D. G. Myszka, and I. A. Laird-Offringa
Two Functionally Distinct Steps Mediate High Affinity Binding of U1A Protein to U1 Hairpin II RNA
J. Biol. Chem., June 8, 2001; 276(24): 21476 - 21481.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the Biophysical Society.