Nucleic Acids Research Advance Access originally published online on February 20, 2007
Nucleic Acids Research 2007 35(5):1698-1713; doi:10.1093/nar/gkm020
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Nucleic Acids Research, 2007, Vol. 35, No. 5 1698-1713
© 2007 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 |
Resolving fast and slow motions in the internal loop containing stem-loop 1 of HIV-1 that are modulated by Mg2+ binding: role in the kissing–duplex structural transition
Department of Chemistry & Biophysics Research Division, The University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109-1055, USA
*To whom correspondence should be addressed. Tel: 734 615 3361; Fax: 734 647 4865; Email: hashimi{at}umich.edu
Received November 20, 2006. Revised December 30, 2006. Accepted January 2, 2007.
Stem loop 1 (SL1) is a highly conserved hairpin in the 5'-leader of the human immunodeficiency virus type I that forms a metastable kissing dimer that is converted during viral maturation into a stable duplex with the aid of the nucleocapsid (NC) protein. SL1 contains a highly conserved internal loop that promotes the kissing–duplex transition by a mechanism that remains poorly understood. Using NMR, we characterized internal motions induced by the internal loop in an SL1 monomer that may promote the kissing–duplex transition. This includes micro-to-millisecond secondary structural transitions that cause partial melting of three base-pairs above the internal loop making them key nucleation sites for exchanging strands and nanosecond rigid-body stem motions that can help bring strands into spatial register. We show that while Mg2+ binds to the internal loop and arrests these internal motions, it preserves and/or activates local mobility at internal loop residues G272 and G273 which are implicated in NC binding. By stabilizing SL1 without compromising the accessibility of G272 and G273 for NC binding, Mg2+ may increase the dependence of the kissing–duplex transition on NC binding thus preventing spontaneous transitions from taking place and ensuring that viral RNA and protein maturation occur in concert.
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