Evidence map›Paper›PMID 27692964›Full record

ArticleStructure (London, England : 1993)2016

The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical.

Meytal Galilee, Elena Britan-Rosich, Sarah L Griner, Serdar Uysal, Viola Baumgärtel, Don C Lamb, Anthony A Kossiakoff, Moshe Kotler, Robert M Stroud, Ailie Marx and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 31% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2Iranian journal of pharmaceutical research : IJPR · 2021
    Article
  2. Article
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

11 authors at 6 institutions in 4 countries.

Meytal GalileeDepartment of Biology, Technion - Israel Institute of Technology, Haifa 320003, Israel.
Elena Britan-RosichDepartment of Immunology and Pathology, The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
Sarah L GrinerDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Serdar UysalDepartment of Biophysics, Bezmialem Vakif University, Istanbul 34093, Turkey.
Viola BaumgärtelPhysical Chemistry, Department of Chemistry, Nanosystem Initiative Munich (NIM), Center for Integrated Protein Science Munich (CiPSM), Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, Munich 81377, Germany.
Don C LambPhysical Chemistry, Department of Chemistry, Nanosystem Initiative Munich (NIM), Center for Integrated Protein Science Munich (CiPSM), Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, Munich 81377, Germany.
Anthony A KossiakoffDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Moshe KotlerDepartment of Immunology and Pathology, The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
Robert M StroudDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Ailie MarxDepartment of Biology, Technion - Israel Institute of Technology, Haifa 320003, Israel.
Akram AlianDepartment of Biology, Technion - Israel Institute of Technology, Haifa 320003, Israel. Electronic address: alian@tx.technion.ac.il.
Technion – Israel Institute of Technology · ILCenter for Integrated Protein Science Munich · DEHebrew University of Jerusalem · ILUniversity of California, San Francisco · USBezmiâlem Vakıf Üniversitesi · TRUniversity of Chicago · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2007 to 2018
$48.8M
Foreign - Univ. of Toronto, PI-Dr. Sachdev SidhuU01GM094588 · NIGMS · UNIVERSITY OF CHICAGO · PI KOSSIAKOFF, ANTHONY A · 2010 to 2014
$6.8M
Chaperone-Assisted Structure Determination of Membrane ProteinsR01GM117372 · NIGMS · UNIVERSITY OF CHICAGO · PI ANTHONY A KOSSIAKOFF · 2016 to 2026
$4.0M
NIGMS NIH HHS P50 GM082250NIGMS NIH HHS R01 GM117372NIGMS NIH HHS U01 GM094588
6 · The paper itself

Abstract

HIV-1 integrase (IN) catalyzes viral DNA integration into the host genome and facilitates multifunctional steps including virus particle maturation. Competency of IN to form multimeric assemblies is functionally critical, presenting an approach for anti-HIV strategies. Multimerization of IN depends on interactions between the distinct subunit domains and among the flanking protomers. Here, we elucidate an overlooked docking cleft of IN core domain that anchors the N-terminal helix-turn-helix (HTH) motif in a highly preserved and functionally critical configuration. Crystallographic structure of IN core domain in complex with Fab specifically targeting this cleft reveals a steric overlap that would inhibit HTH-docking, C-terminal domain contacts, DNA binding, and subsequent multimerization. While Fab inhibits in vitro IN integration activity, in vivo it abolishes virus particle production by specifically associating with preprocessed IN within Gag-Pol and interfering with early cytosolic Gag/Gag-Pol assemblies. The HTH-docking cleft may offer a fresh hotspot for future anti-HIV intervention strategies.

Indexed as

Catalytic DomainCrystallography, X-RayHelix-Turn-Helix MotifsHIV-1HIV IntegraseModels, MolecularMolecular Docking SimulationProtein BindingProtein MultimerizationProtein Structure, SecondaryRNA, ViralHIV IntegraseRNA, Viral

Identifiers

PMID27692964
PMCPMC5093063
OpenAlexW2527278243

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.