Evidence map›Paper›PMID 37184020›Full record

ArticleThe Journal of chemical physics2023

Domain tethering impacts dimerization and DNA-mediated allostery in the human transcription factor FoxP1.

Perla Cruz, Nicolás Paredes, Isabel Asela, Narendar Kolimi, José Alejandro Molina, César A Ramírez-Sarmiento, Rajen Goutam, Gangton Huang, Exequiel Medina, Hugo Sanabria

Open access · hybridAbstract read
In one paragraph

Article in The Journal of chemical physics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

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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

10 authors at 3 institutions in 2 countries.

Perla CruzDepartamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Santiago 7800003, Chile.
Nicolás ParedesDepartamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Santiago 7800003, Chile.
Isabel AselaDepartamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Santiago 7800003, Chile.
Narendar KolimiDepartment of Physics and Astronomy, Clemson University, Clemson, South Carolina 29634, USA.ORCID 0000-0003-4118-8794
José Alejandro MolinaInstitute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Santiago 7820436, Chile.ORCID 0009-0006-2235-6376
César A Ramírez-SarmientoInstitute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Santiago 7820436, Chile.ORCID 0000-0003-4647-903X
Rajen GoutamDepartment of Physics and Astronomy, Clemson University, Clemson, South Carolina 29634, USA.ORCID 0009-0006-4080-7193
Gangton HuangDepartment of Physics and Astronomy, Clemson University, Clemson, South Carolina 29634, USA.ORCID 0000-0001-8631-7014
Exequiel MedinaDepartamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Santiago 7800003, Chile.ORCID 0000-0002-1040-6720
Hugo SanabriaDepartment of Physics and Astronomy, Clemson University, Clemson, South Carolina 29634, USA.ORCID 0000-0001-7068-6827
Clemson University · USUniversity of Chile · CLPontificia Universidad Católica de Chile · CL

Funding

SINGLE MOLECULE ANALYSIS OF PSD-95 STRUCTURE AND LIGAND BINDINGR01MH081923 · NIMH · STATE UNIVERSITY NEW YORK STONY BROOK · PI BOWEN, MARK E · 2008 to 2022
$5.6M
NIMH NIH HHS R01 MH081923
6 · The paper itself

Abstract

Transcription factors are multidomain proteins with specific DNA binding and regulatory domains. In the human FoxP subfamily (FoxP1, FoxP2, FoxP3, and FoxP4) of transcription factors, a 90 residue-long disordered region links a Leucine Zipper (ZIP)-known to form coiled-coil dimers-and a Forkhead (FKH) domain-known to form domain swapping dimers. We used replica exchange discrete molecular dynamics simulations, single-molecule fluorescence experiments, and other biophysical tools to understand how domain tethering in FoxP1 impacts dimerization at ZIP and FKH domains and how DNA binding allosterically regulates their dimerization. We found that domain tethering promotes FoxP1 dimerization but inhibits a FKH domain-swapped structure. Furthermore, our findings indicate that the linker mediates the mutual organization and dynamics of ZIP and FKH domains, forming closed and open states with and without interdomain contacts, thus highlighting the role of the linkers in multidomain proteins. Finally, we found that DNA allosterically promotes structural changes that decrease the dimerization propensity of FoxP1. We postulate that, upon DNA binding, the interdomain linker plays a crucial role in the gene regulatory function of FoxP1.

Indexed as

DNATranscription FactorsDimerizationForkhead Transcription FactorsGene Expression RegulationHumansProtein DomainsRepressor ProteinsDNAForkhead Transcription FactorsFOXP1 protein, humanFOXP4 protein, humanRepressor ProteinsTranscription Factors

Identifiers

PMID37184020
PMCPMC10188207
OpenAlexW4376616737

What OpenQuestion holds

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LicenceCC BY
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.