Nucleic Acids Research Advance Access originally published online on January 12, 2009
Nucleic Acids Research 2009 37(5):1529-1540; doi:10.1093/nar/gkn1074
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2009, Vol. 37, No. 5 1529-1540
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
How binding of small molecule and peptide ligands to HIV-1 TAR alters the RNA motional landscape
1Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA, 2Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland and 3Department of Biochemistry, University of Washington, Seattle, WA 98195-1700, USA
*To whom correspondence should be addressed. Tel: +1 206 543 7113; Fax: +1 206 685 8665; Email: varani{at}chem.washington.edu
Received November 3, 2008. Revised December 18, 2008. Accepted December 22, 2008.
The HIV-1 TAR RNA represents a well-known paradigm to study the role of dynamics and conformational change in RNA function. This regulatory RNA changes conformation in response to binding of Tat protein and of a variety of peptidic and small molecule ligands, indicating that its conformational flexibility and intrinsic dynamics play important roles in molecular recognition. We have used 13C NMR relaxation experiments to examine changes in the motional landscape of HIV-1 TAR in the presence of three ligands of different affinity and specificity. The ligands are argininamide, a linear peptide mimic of the Tat basic domain and a cyclic peptide that potently inhibits Tat-dependent activation of transcription. All three molecules induce the same motional characteristics within the three nucleotides bulge that represents the Tat-binding site. However, the cyclic peptide has a unique motional signature in the apical loop, which represents a binding site for the essential host co-factor cyclin T1. These results suggest that all peptidic mimics of Tat induce the same dynamics in TAR within this protein binding site. However, the new cyclic peptide mimic of Tat represents a new class of ligands with a unique effect on the dynamics and the structure of the apical loop.
Present address: Zahra Shajani, Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines, La Jolla, CA 92037, USA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Q. Zhang and H. M. Al-Hashimi Domain-elongation NMR spectroscopy yields new insights into RNA dynamics and adaptive recognition RNA, November 1, 2009; 15(11): 1941 - 1948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Davidson, T. C. Leeper, Z. Athanassiou, K. Patora-Komisarska, J. Karn, J. A. Robinson, and G. Varani Simultaneous recognition of HIV-1 TAR RNA bulge and loop sequences by cyclic peptide mimics of Tat protein PNAS, July 21, 2009; 106(29): 11931 - 11936. [Abstract] [Full Text] [PDF]
|
|