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
[21]   MAPPING DOMAINS OF RETROVIRAL INTEGRASE RESPONSIBLE FOR VIRAL-DNA SPECIFICITY AND TARGET SITE SELECTION BY ANALYSIS OF CHIMERAS BETWEEN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND VISNA VIRUS INTEGRASES [J].
KATZMAN, M ;
SUDOL, M .
JOURNAL OF VIROLOGY, 1995, 69 (09) :5687-5696
[22]   ACTIVITIES AND SUBSTRATE-SPECIFICITY OF THE EVOLUTIONARILY CONSERVED CENTRAL DOMAIN OF RETROVIRAL INTEGRASE [J].
KULKOSKY, J ;
KATZ, RA ;
MERKEL, G ;
SKALKA, AM .
VIROLOGY, 1995, 206 (01) :448-456
[23]   RESIDUES CRITICAL FOR RETROVIRAL INTEGRATIVE RECOMBINATION IN A REGION THAT IS HIGHLY CONSERVED AMONG RETROVIRAL RETROTRANSPOSON INTEGRASES AND BACTERIAL INSERTION-SEQUENCE TRANSPOSASES [J].
KULKOSKY, J ;
JONES, KS ;
KATZ, RA ;
MACK, JPG ;
SKALKA, AM .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (05) :2331-2338
[24]   SUBSTRATE-SPECIFICITY OF RECOMBINANT HUMAN-IMMUNODEFICIENCY-VIRUS INTEGRASE PROTEIN [J].
LAFEMINA, RL ;
CALLAHAN, PL ;
CORDINGLEY, MG .
JOURNAL OF VIROLOGY, 1991, 65 (10) :5624-5630
[25]   BOTH SUBSTRATE AND TARGET OLIGONUCLEOTIDE SEQUENCES AFFECT INVITRO INTEGRATION MEDIATED BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE PROTEIN PRODUCED IN SACCHAROMYCES-CEREVISIAE [J].
LEAVITT, AD ;
ROSE, RB ;
VARMUS, HE .
JOURNAL OF VIROLOGY, 1992, 66 (04) :2359-2368
[26]  
LEAVITT AD, 1993, J BIOL CHEM, V268, P2113
[27]  
MULLER HP, 1994, EMBO J, V13, P4707
[28]   CHARACTERIZATION OF THE HUMAN SPUMA RETROVIRUS INTEGRASE BY SITE-DIRECTED MUTAGENESIS, BY COMPLEMENTATION ANALYSIS, AND BY SWAPPING THE ZINC-FINGER DOMAIN OF HIV-1 [J].
PAHL, A ;
FLUGEL, RM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (07) :2957-2966
[29]  
PRUSS D, 1994, J BIOL CHEM, V269, P25031
[30]   HUMAN-IMMUNODEFICIENCY-VIRUS INTEGRASE DIRECTS INTEGRATION TO SITES OF SEVERE DNA DISTORTION WITHIN THE NUCLEOSOME CORE [J].
PRUSS, D ;
BUSHMAN, FD ;
WOLFFE, AP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (13) :5913-5917