The core domain of HIV-1 integrase recognizes key features of its DNA substrates

被引:47
作者
Gerton, JL
Brown, PO
机构
[1] STANFORD UNIV,MED CTR,HOWARD HUGHES MED INST,STANFORD,CA 94305
[2] STANFORD UNIV,MED CTR,DEPT BIOCHEM,STANFORD,CA 94305
[3] STANFORD UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305
关键词
D O I
10.1074/jbc.272.41.25809
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated which features of the substrate specificity of human immunodeficiency virus type 1 (HIV-1) integrase could be assigned to the central domain of the 288-residue HIV-1 integrase protein, composed of amino acids 50-212. This domain contains the active site and shares structural homology with a large family of polynucleotidyl transferases. Using model substrates with defined alterations in critical features we found that this domain alone is sufficient for recognition of: 1) the phylogenetically conserved CA/TG base pairs near the viral DNA end; 2) the 5'-terminal dinucleotide that is left unpaired after end processing; and 3) target DNA flanking the site of joining. Future efforts aimed at identifying specific amino acids involved in recognition of these key substrate features can now be targeted at this domain.
引用
收藏
页码:25809 / 25815
页数:7
相关论文
共 45 条
[11]   IDENTIFICATION OF AMINO-ACID-RESIDUES CRITICAL FOR ENDONUCLEASE AND INTEGRATION ACTIVITIES OF HIV-1 IN PROTEIN INVITRO [J].
DRELICH, M ;
WILHELM, R ;
MOUS, J .
VIROLOGY, 1992, 188 (02) :459-468
[12]   CRYSTAL-STRUCTURE OF THE CATALYTIC DOMAIN OF HIV-1 INTEGRASE - SIMILARITY TO OTHER POLYNUCLEOTIDYL TRANSFERASES [J].
DYDA, F ;
HICKMAN, AB ;
JENKINS, TM ;
ENGELMAN, A ;
CRAIGIE, R ;
DAVIES, DR .
SCIENCE, 1994, 266 (5193) :1981-1986
[13]   A STABLE COMPLEX BETWEEN INTEGRASE AND VIRAL-DNA ENDS MEDIATES HUMAN-IMMUNODEFICIENCY-VIRUS INTEGRATION IN-VITRO [J].
ELLISON, V ;
BROWN, PO .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (15) :7316-7320
[14]   AN ESSENTIAL INTERACTION BETWEEN DISTINCT DOMAINS OF HIV-1 INTEGRASE MEDIATES ASSEMBLY OF THE ACTIVE MULTIMER [J].
ELLISON, V ;
GERTON, J ;
VINCENT, KA ;
BROWN, PO .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (07) :3320-3326
[15]   IDENTIFICATION OF DISCRETE FUNCTIONAL DOMAINS OF HIV-1 INTEGRASE AND THEIR ORGANIZATION WITHIN AN ACTIVE MULTIMERIC COMPLEX [J].
ENGELMAN, A ;
BUSHMAN, FD ;
CRAIGIE, R .
EMBO JOURNAL, 1993, 12 (08) :3269-3275
[16]   THE CORE AND CARBOXYL-TERMINAL DOMAINS OF THE INTEGRASE PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EACH CONTRIBUTE TO NONSPECIFIC DNA-BINDING [J].
ENGELMAN, A ;
HICKMAN, AB ;
CRAIGIE, R .
JOURNAL OF VIROLOGY, 1994, 68 (09) :5911-5917
[17]  
ENGLEMAN A, 1992, J VIROL, V66, P6361
[18]   RETROVIRAL DNA INTEGRATED DURING INFECTION BY AN INTEGRATION-DEFICIENT MUTANT OF MURINE LEUKEMIA-VIRUS IS OLIGOMERIC [J].
HAGINOYAMAGISHI, K ;
DONEHOWER, LA ;
VARMUS, HE .
JOURNAL OF VIROLOGY, 1987, 61 (06) :1964-1971
[19]   CATALYTIC DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE - IDENTIFICATION OF A SOLUBLE MUTANT BY SYSTEMATIC REPLACEMENT OF HYDROPHOBIC RESIDUES [J].
JENKINS, TM ;
HICKMAN, AB ;
DYDA, F ;
GHIRLANDO, R ;
DAVIES, DR ;
CRAIGIE, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (13) :6057-6061
[20]   A soluble active mutant of HIV-1 integrase - Involvement of both the core and carboxyl-terminal domains in multimerization [J].
Jenkins, TM ;
Engelman, A ;
Ghirlando, R ;
Craigie, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7712-7718