Evidence map›Paper›PMID 18093980›Full record

ArticleThe Journal of biological chemistry2008

Subunit-specific protein footprinting reveals significant structural rearrangements and a role for N-terminal Lys-14 of HIV-1 Integrase during viral DNA binding.

Zhuojun Zhao, Christopher J McKee, Jacques J Kessl, Webster L Santos, Janet E Daigle, Alan Engelman, Gregory Verdine, Mamuka Kvaratskhelia

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 50 citations in OpenAlex.

  1. HIV-1 Integrase Inhibition Activity by Spiroketals Derived fromPharmaceuticals (Basel, Switzerland) · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Zhuojun ZhaoCenter for Retrovirus Research and Comprehensive Cancer Center, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Christopher J McKee
Jacques J Kessl
Webster L Santos
Janet E Daigle
Alan Engelman
Gregory Verdine
Mamuka Kvaratskhelia
The Ohio State University · USHarvard University · USDana-Farber Cancer Institute · US

Funding

Biochemical Mechanism of HIV DNA IntegrationR37AI039394 · NIAID · DANA-FARBER CANCER INST · PI Alan N. Engelman · 2010 to 2026
$10.2M
Structure and function of HIV-1 integraseR01AI062520 · NIAID · UNIVERSITY OF COLORADO DENVER · PI KVARATSKHELIA, MAMUKA · 2006 to 2020
$5.3M
FUNCTIONALLY TETHERED OLIGONUCLEOTIDESR01GM044853 · NIGMS · HARVARD UNIVERSITY · PI VERDINE, GREGORY LAWRENCE · 1990 to 2011
$5.1M
BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATIONR01AI039394 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 1996 to 2009
$3.8M
Peptide Morphing: Rational Design of Separase InhibitorsF32GM067380 · NIGMS · HARVARD UNIVERSITY · PI SANTOS, WEBSTER L · 2003 to 2005
$131k
NIAID NIH HHS AI039394NIAID NIH HHS AI062520NIAID NIH HHS R01 AI039394NIAID NIH HHS R01 AI062520NIAID NIH HHS R37 AI039394NIGMS NIH HHS F32 GM067380NIGMS NIH HHS R01 GM044853
6 · The paper itself

Abstract

To identify functional contacts between HIV-1 integrase (IN) and its viral DNA substrate, we devised a new experimental strategy combining the following two methodologies. First, disulfide-mediated cross-linking was used to site-specifically link select core and C-terminal domain amino acids to respective positions in viral DNA. Next, surface topologies of free IN and IN-DNA complexes were compared using Lys- and Arg-selective small chemical modifiers and mass spectrometric analysis. This approach enabled us to dissect specific contacts made by different monomers within the multimeric complex. The foot-printing studies for the first time revealed the importance of a specific N-terminal domain residue, Lys-14, in viral DNA binding. In addition, a DNA-induced conformational change involving the connection between the core and C-terminal domains was observed. Site-directed mutagenesis experiments confirmed the importance of the identified contacts for recombinant IN activities and virus infection. These new findings provided major constraints, enabling us to identify the viral DNA binding channel in the active full-length IN multimer. The experimental approach described here has general application to mapping interactions within functional nucleoprotein complexes.

Indexed as

Amino Acid SubstitutionCell LineDNA, ViralHIV-1HIV InfectionsHIV IntegraseHumansMutagenesis, Site-DirectedPeptide MappingProtein Structure, QuaternaryProtein Structure, TertiaryDNA, ViralHIV Integrase

Identifiers

PMID18093980
PMCPMC2806305
OpenAlexW2077728594

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.