Nucleic acid binding and chaperone properties of HIV-1 Gag and nucleocapsid proteins - Aggregation & Cleavage

Nucleic acid binding and chaperone properties of HIV-1 Gag and nucleocapsid proteins
Received December 5, 2005; Revised January 5, 2006; Accepted January 5, 2006.
Published online 2006 January 30.
Margareta Cruceanu,1 Maria A. Urbaneja,2 Catherine V. Hixson,2 Donald G. Johnson,2 Siddhartha A. Datta,3 Matthew J. Fivash,4 Andrew G. Stephen,5 Robert J. Fisher,5 Robert J. Gorelick,2 Jose R. Casas-Finet,6 Alan Rein,3 Ioulia Rouzina,7 and Mark C. Williams1,8*
Nucleic Acids Research
PubMed Central
Copyright ? The Author 2006. Published by Oxford University Press. All rights reserved
1Department of Physics, Northeastern University, 111 Dana Research Center, 110 Forsyth Street, Boston, MA 02115, USA
2AIDS Vaccine Program, SAIC-Frederick, Inc., NCI at Frederick, Frederick, MD 21702, USA
3HIV Drug Resistance Program, NCI-Frederick, Frederick, MD 21702-1201, USA
4Data Management Services, Inc., NCI-Frederick, Frederick, MD 2170, USA
5Protein Chemistry Laboratory, SAIC Frederick, Inc., NCI at Frederick, Frederick, MD 2170, USA
6MedImmune, Inc., 35 W. Watkins Mill Road, Gaithersburg, MD 20878, USA
7Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 6-155 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA
8Center for Interdisciplinary Research on Complex Systems, Northeastern University, 111 Dana Research Center, 110 Forsyth Street, Boston, MA 02115, USA
*To whom correspondence should be addressed. Tel: 1 617 373 7323; Fax: 1 617 373 2943; Email: mark@neu.edu
Correspondence may also be addressed to Ioulia Rouzina. Tel: 1 612 624 7468; Fax: 1 612 624 5121; Email: rouzina@cbs.umn.edu
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Abstract
The Gag polyprotein of HIV-1 is essential for retroviral replication and packaging. The nucleocapsid (NC) protein is the primary region for the interaction of Gag with nucleic acids. In this study, we examine the interactions of Gag and its NC cleavage products (NCp15, NCp9 and NCp7) with nucleic acids using solution and single molecule experiments. The NC cleavage products bound DNA with comparable affinity and strongly destabilized the DNA duplex. In contrast, the binding constant of Gag to DNA was found to be ~10-fold higher than that of the NC proteins, and its destabilizing effect on dsDNA was negligible. These findings are consistent with the primary function of Gag as a nucleic acid binding and packaging protein and the primary function of the NC proteins as nucleic acid chaperones. Also, our results suggest that NCp7's capability for fast sequence-nonspecific nucleic acid duplex destabilization, as well as its ability to facilitate nucleic acid strand annealing by inducing electrostatic attraction between strands, likely optimize the fully processed NC protein to facilitate complex nucleic acid secondary structure rearrangements. In contrast, Gag's stronger DNA binding and aggregation capabilities likely make it an effective chaperone for processes that do not require significant duplex destabilization
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