Evidence map›Paper›PMID 32681840›Full record

ArticleJournal of molecular biology2020

Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.

Xiao Lei, Jun Zhao, Jared M Sagendorf, Niroop Rajashekar, Jiang Xu, Ana Carolina Dantas Machado, Chandani Sen, Remo Rohs, Pinghui Feng, Lin Chen

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

Article in Journal of molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 46% 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, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  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

10 authors at 1 institution in 1 country.

Xiao LeiMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: xiaoleiusc@gmail.com.
Jun ZhaoSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, 925 W 34th Street, Los Angeles, CA 90089, USA.
Jared M SagendorfQuantitative and Computational Biology, Departments of Biological Sciences, Physics & Astronomy, and Computer Science, University of Southern California, Los Angeles, CA 90089, USA.
Niroop RajashekarMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Jiang XuMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Ana Carolina Dantas MachadoQuantitative and Computational Biology, Departments of Biological Sciences, Physics & Astronomy, and Computer Science, University of Southern California, Los Angeles, CA 90089, USA.
Chandani SenMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Remo RohsDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089, USA; USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Quantitative and Computational Biology, Departments of Biological Sciences, Physics & Astronomy, and Computer Science, University of Southern California, Los Angeles, CA 90089, USA.
Pinghui FengSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, 925 W 34th Street, Los Angeles, CA 90089, USA.
Lin ChenMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA; USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: linchen@usc.edu.
University of Southern California · US

Funding

Mapping the 3D Genome LandscapeU54DK107981 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ALBER, FRANK, CHEN, LIN · 2015 to 2019
$4.2M
Quantitative Modeling of Transcription Factor-DNA BindingR35GM130376 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Remo Rohs · 2019 to 2026
$3.3M
Explore FOXP3's role in the 3D organization of the genomeR01AI113009 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, LIN · 2015 to 2019
$1.9M
Image-directed nanoscale photo-crosslinking for the study of sub-nuclear structuresR21HG010528 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, LIN · 2019 to 2020
$454k
NHGRI NIH HHS R21 HG010528NIAID NIH HHS R01 AI113009NIDDK NIH HHS U54 DK107981NIGMS NIH HHS R35 GM130376
6 · The paper itself

Abstract

MEF2 and NKX2-5 transcription factors interact with each other in cardiogenesis and are necessary for normal heart formation. Despite evidence suggesting that these two transcription factors function synergistically and possibly through direct physical interactions, molecular mechanisms by which they interact are not clear. Here we determined the crystal structures of ternary complexes of MEF2 and NKX2-5 bound to myocardin enhancer DNA in two crystal forms. These crystal structures are the first example of human MADS-box/homeobox ternary complex structures involved in cardiogenesis. Our structures reveal two possible modes of interactions between MEF2 and NKX2-5: MEF2 and NKX bind to adjacent DNA sites to recognize DNA in cis; and MEF2 and NKX bind to different DNA strands to interact with each other in trans via a conserved protein-protein interface observed in both crystal forms. Disease-related mutations are mapped to the observed protein-protein interface. Our structural studies provide a starting point to understand and further study the molecular mechanisms of the interactions between MEF2 and NKX2.5 and their roles in cardiogenesis.

Indexed as

Amino Acid SequenceBinding SitesCrystallography, X-RayDNAHomeobox Protein Nkx-2.5HumansMEF2 Transcription FactorsMolecular Docking SimulationProtein BindingProtein Interaction Domains and MotifsProtein Interaction MapsDNAHomeobox Protein Nkx-2.5MEF2B protein, humanMEF2 Transcription FactorsNKX2-5 protein, humancardiogenesisMEF2NKX2–5protein–protein interactiontranscription regulation

Identifiers

PMID32681840
PMCPMC8099449
OpenAlexW3042985605

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.