Evidence map›Paper›PMID 26829219›Full record

ArticleJournal of molecular biology2016

Dlx5 Homeodomain:DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome.

Andrew Proudfoot, Herbert L Axelrod, Michael Geralt, Robert J Fletterick, Fumiaki Yumoto, Ashley M Deacon, Marc-André Elsliger, Ian A Wilson, Kurt Wüthrich, Pedro Serrano

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular biology, 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
0.9field-weighted citation impact, top 24% 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, 10 citations in OpenAlex.

  1. Salt Dependence of DNA Binding Activity of Human Transcription Factor Dlx3.International journal of molecular sciences · 2022
    Article
  2. Allelic Switching ofInternational journal of genomics · 2019
    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

10 authors at 4 institutions in 2 countries.

Andrew ProudfootDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Herbert L AxelrodStanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
Michael GeraltDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Robert J FletterickDepartment of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
Fumiaki YumotoDepartment of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
Ashley M DeaconStanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
Marc-André ElsligerDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Kurt WüthrichDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Institute of Molecular Biology and Biophysics, ETH Zürich, CH 8093, Zürich, Switzerland.
Pedro SerranoDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: serrano@scripps.edu.
Scripps Research Institute · USUniversity of California, San Francisco · USSLAC National Accelerator Laboratory · USStanford Synchrotron Radiation Lightsource · US

Funding

Structure Determination Core at SSRLU54GM094586 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI WOOLEY, JOHN C · 2010 to 2014
$40.1M
ZWITTERION SURFACTANT DDMAB FOR IMPROV STABIL OF PROTEINP41RR001209 · NCRR · STANFORD UNIVERSITY · PI GONZALEZ, ANA M · 1985 to 2011
$38.9M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Structures of Protein Complexes Regulating Transcription in Enbryonic Stem CellsU01GM094614 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CONKLIN, BRUCE R · 2010 to 2014
$5.7M
NCRR NIH HHS P41 RR001209NCRR NIH HHS P41RR001209NIGMS NIH HHS P41 GM103393NIGMS NIH HHS P41GM103393NIGMS NIH HHS U01 GM094614NIGMS NIH HHS U54 GM094586
6 · The paper itself

Abstract

The Dlx5 homeodomain is a transcription factor related to the Drosophila distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including split hand and foot malformation 1 in humans. Our characterization of a Dlx5 homeodomain:(CGACTAATTAGTCG)2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A Q186H mutation linked to split hand and foot malformation 1 likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and they likely destabilize the formation of functional complexes.

Indexed as

Crystallography, X-RayDNAHomeodomain ProteinsHumansLimb Deformities, CongenitalMagnetic Resonance SpectroscopyModels, MolecularMutant ProteinsMutation, MissenseNucleic Acid ConformationProtein BindingProtein ConformationTranscription FactorsDLX5 protein, humanDNAHomeodomain ProteinsMutant ProteinsTranscription FactorsNMR spectroscopyprotein:DNA complexSHFM-1 syndrome

Identifiers

PMID26829219
PMCPMC4826628
OpenAlexW2252449038

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.