An amino acid in the central catalytic domain of three retroviral integrases that affects target site selection in nonviral DNA

Amy L. Harper, Malgorzata Sudol, Michael Katzman

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Integrase can insert retroviral DNA into almost any site in cellular DNA; however, target site preferences are noted in vitro and in vivo. We recently demonstrated that amino acid 119, in the α2 helix of the central domain of the human immunodeficiency virus type 1 integrase, affected the choice of nonviral target DNA sites. We have now extended these findings to the integrases of a nonprimate lentivirus and a more distantly related alpharetrovirus. We found that substitutions at the analogous positions in visna virus integrase and Rous sarcoma virus integrase changed the target site preferences in five assays that monitor insertion into nonviral DNA. Thus, the importance of this protein residue in the selection of nonviral target DNA sites is likely to be a general property of retroviral integrases. Moreover, this amino acid might be part of the cellular DNA binding site on integrase proteins.

Original languageEnglish (US)
Pages (from-to)3838-3845
Number of pages8
JournalJournal of virology
Volume77
Issue number6
DOIs
StatePublished - Mar 1 2003

Fingerprint

Integrases
active sites
Catalytic Domain
Amino Acids
amino acids
DNA
Alpharetrovirus
Visna maedi virus
Rous sarcoma virus
Visna-maedi virus
Lentivirus
Human immunodeficiency virus 1
binding sites
proteins
HIV-1
Proteins
Binding Sites
assays

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

@article{7f70c82e86904e1d85d1fa1a7d1d8885,
title = "An amino acid in the central catalytic domain of three retroviral integrases that affects target site selection in nonviral DNA",
abstract = "Integrase can insert retroviral DNA into almost any site in cellular DNA; however, target site preferences are noted in vitro and in vivo. We recently demonstrated that amino acid 119, in the α2 helix of the central domain of the human immunodeficiency virus type 1 integrase, affected the choice of nonviral target DNA sites. We have now extended these findings to the integrases of a nonprimate lentivirus and a more distantly related alpharetrovirus. We found that substitutions at the analogous positions in visna virus integrase and Rous sarcoma virus integrase changed the target site preferences in five assays that monitor insertion into nonviral DNA. Thus, the importance of this protein residue in the selection of nonviral target DNA sites is likely to be a general property of retroviral integrases. Moreover, this amino acid might be part of the cellular DNA binding site on integrase proteins.",
author = "Harper, {Amy L.} and Malgorzata Sudol and Michael Katzman",
year = "2003",
month = "3",
day = "1",
doi = "10.1128/JVI.77.6.3838-3845.2003",
language = "English (US)",
volume = "77",
pages = "3838--3845",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "6",

}

An amino acid in the central catalytic domain of three retroviral integrases that affects target site selection in nonviral DNA. / Harper, Amy L.; Sudol, Malgorzata; Katzman, Michael.

In: Journal of virology, Vol. 77, No. 6, 01.03.2003, p. 3838-3845.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An amino acid in the central catalytic domain of three retroviral integrases that affects target site selection in nonviral DNA

AU - Harper, Amy L.

AU - Sudol, Malgorzata

AU - Katzman, Michael

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Integrase can insert retroviral DNA into almost any site in cellular DNA; however, target site preferences are noted in vitro and in vivo. We recently demonstrated that amino acid 119, in the α2 helix of the central domain of the human immunodeficiency virus type 1 integrase, affected the choice of nonviral target DNA sites. We have now extended these findings to the integrases of a nonprimate lentivirus and a more distantly related alpharetrovirus. We found that substitutions at the analogous positions in visna virus integrase and Rous sarcoma virus integrase changed the target site preferences in five assays that monitor insertion into nonviral DNA. Thus, the importance of this protein residue in the selection of nonviral target DNA sites is likely to be a general property of retroviral integrases. Moreover, this amino acid might be part of the cellular DNA binding site on integrase proteins.

AB - Integrase can insert retroviral DNA into almost any site in cellular DNA; however, target site preferences are noted in vitro and in vivo. We recently demonstrated that amino acid 119, in the α2 helix of the central domain of the human immunodeficiency virus type 1 integrase, affected the choice of nonviral target DNA sites. We have now extended these findings to the integrases of a nonprimate lentivirus and a more distantly related alpharetrovirus. We found that substitutions at the analogous positions in visna virus integrase and Rous sarcoma virus integrase changed the target site preferences in five assays that monitor insertion into nonviral DNA. Thus, the importance of this protein residue in the selection of nonviral target DNA sites is likely to be a general property of retroviral integrases. Moreover, this amino acid might be part of the cellular DNA binding site on integrase proteins.

UR - http://www.scopus.com/inward/record.url?scp=0037334017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037334017&partnerID=8YFLogxK

U2 - 10.1128/JVI.77.6.3838-3845.2003

DO - 10.1128/JVI.77.6.3838-3845.2003

M3 - Article

C2 - 12610159

AN - SCOPUS:0037334017

VL - 77

SP - 3838

EP - 3845

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 6

ER -