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

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1997年 / 272卷 / 41期

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

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页码：25809 / 25815

页数：7

相关论文

共 45 条

[1] IN-VITRO INTEGRATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CDNA INTO TARGETS CONTAINING PROTEIN-INDUCED BENDS [J].

BOR, YC ;

BUSHMAN, FD ;

ORGEL, LE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (22) :10334-10338

[2]

Brown P.O., 1997, Retroviruses

[3] CORRECT INTEGRATION OF RETROVIRAL DNA INVITRO [J].

BROWN, PO ;

BOWERMAN, B ;

VARMUS, HE ;

BISHOP, JM .

CELL, 1987, 49 (03) :347-356

[4] The catalytic domain of avian sarcoma virus integrase: Conformation of the active-site residues in the presence of divalent cations [J].

Bujacz, G ;

Jaskolski, M ;

Alexandratos, J ;

Wlodawer, A ;

Merkel, G ;

Katz, RA ;

Skalka, AM .

STRUCTURE, 1996, 4 (01) :89-96

[5] DOMAINS OF THE INTEGRASE PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RESPONSIBLE FOR POLYNUCLEOTIDYL TRANSFER AND ZINC-BINDING [J].

BUSHMAN, FD ;

ENGELMAN, A ;

PALMER, I ;

WINGFIELD, P ;

CRAIGIE, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (08) :3428-3432

[6] ACTIVITIES OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INTEGRATION PROTEIN INVITRO - SPECIFIC CLEAVAGE AND INTEGRATION OF HIV DNA [J].

BUSHMAN, FD ;

CRAIGIE, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (04) :1339-1343

[7] SUBSTRATE FEATURES IMPORTANT FOR RECOGNITION AND CATALYSIS BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE IDENTIFIED BY USING NOVEL DNA SUBSTRATES [J].

CHOW, SA ;

BROWN, PO .

JOURNAL OF VIROLOGY, 1994, 68 (06) :3896-3907

[8] REVERSAL OF INTEGRATION AND DNA SPLICING MEDIATED BY INTEGRASE OF HUMAN-IMMUNODEFICIENCY-VIRUS [J].

CHOW, SA ;

VINCENT, KA ;

ELLISON, V ;

BROWN, PO .

SCIENCE, 1992, 255 (5045) :723-726

[9] JUXTAPOSITION OF 2 VIRAL-DNA ENDS IN A BIMOLECULAR DISINTEGRATION REACTION MEDIATED BY MULTIMERS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 OR MURINE LEUKEMIA-VIRUS INTEGRASE [J].

CHOW, SA ;

BROWN, PO .

JOURNAL OF VIROLOGY, 1994, 68 (12) :7869-7878

[10] THE IN PROTEIN OF MOLONEY MURINE LEUKEMIA-VIRUS PROCESSES THE VIRAL-DNA ENDS AND ACCOMPLISHES THEIR INTEGRATION INVITRO [J].

CRAIGIE, R ;

FUJIWARA, T ;

BUSHMAN, F .

CELL, 1990, 62 (04) :829-837

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