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Originally published In Press as doi:10.1074/jbc.M301041200 on July 8, 2003

J. Biol. Chem., Vol. 278, Issue 41, 40385-40391, October 10, 2003
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Rev Binds Specifically to a Purine Loop in the SL1 Region of the HIV-1 Leader RNA*,

Jose Gallego {ddagger} §, Jane Greatorex ¶, Hui Zhang ||, Bin Yang ||, Shyamala Arunachalam ||, Jianhua Fang ||, John Seamons ¶, Susan Lea **, Roger J. Pomerantz || and Andrew M. L. Lever ¶ {ddagger}{ddagger}

From the {ddagger}Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, the University of Cambridge Department of Medicine, Addenbrooke's Hospital, Cambridge, CB2 2QQ, United Kingdom, the ||Center for Human Virology, Division of Infectious Diseases, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5587, and the **Laboratory of Molecular Biophysics, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom

The leader RNA sequence of human immunodeficiency virus type 1 (HIV-1) consists of a complex series of stem loop structures that are critical for viral replication. Three-dimensional structural analysis by NMR of one of these structures, the SL1 stem loop of the packaging signal region, revealed a highly conserved purine rich loop with a structure nearly identical to the Rev-binding loop of the Rev response element. Using band-shift assays, surface plasmon resonance, and further NMR analysis, we demonstrate that this loop binds Rev. HIV-1 appears to have a second Rev-binding site close to the major splice donor site that may have an additional role in the viral life cycle.


Received for publication, January 30, 2003 , and in revised form, July 1, 2003.

* This work was supported by United States Public Health Service Grant AI43876 (to R. J. P.) and by MRC Program Grant G9805564 and the Sykes' Trust (to A. M. L. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

§ Present address: Medivir UK Ltd., Peterhouse Technology Park, 100 Fulbourn Rd., Cambridge CB1 9PT, UK.

{ddagger}{ddagger} To whom correspondence should be addressed. Tel.: 44-1223-336747; Fax: 44-1223-336846; E-mail: amll1{at}mole.bio.cam.ac.uk.


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