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J. Biol. Chem., Vol. 276, Issue 49, 45848-45855, December 7, 2001
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From the Department of Molecular and Medical Pharmacology,
Molecular Biology Institute, and UCLA AIDS Institute, UCLA School of
Medicine, Los Angeles, California 90095
Retroviral integrase plays an important role in
choosing host chromosomal sites for integration of the cDNA copy of
the viral genome. The domain responsible for target site selection has
been previously mapped to the central core of the protein (amino acid residues 49-238). Chimeric integrases between human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) were prepared to examine the involvement of a nonspecific DNA-binding region
(residues 213-266) and certain
Role of the Nonspecific DNA-binding Region and
Helices within
the Core Domain of Retroviral Integrase in Selecting Target DNA Sites
for Integration*
,
helices within the core domain in
target site selection. Determination of the distribution and frequency
of integration events of the chimeric integrases narrowed the target
site-specifying motif to within residues 49-187 and showed that 3
and 4 helices (residues 123-166) were not involved in target site
selection. Furthermore, the chimera with the 2 helix (residues
118-121) of FIV identity displayed characteristic integration events
from both HIV-1 and FIV integrases. The results indicate that the 2
helix plays a role in target site preference as either part of a larger
or multiple target site-specifying motif.
*
This work was supported in part by National Institutes of
Health Grant R01 CA68859.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of an Esther Hayes Student Research Award from the UCLA
AIDS Institute (National Institutes of Health Grant AI28697).
§
Visiting Professor, Department of Biotechnology, Chung-Ang
University, S. Korea.
To whom correspondence should be addressed: Dept. of Molecular
and Medical Pharmacology, Molecular Biology Institute and UCLA AIDS
Institute, UCLA School of Medicine, 23-133 CHS, 10833 Le Conte Ave.,
Los Angeles, CA 90095. Tel.: 310-825-9600; Fax: 310-825-6267; E-mail:
schow@mednet.ucla.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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