Evidence map›Paper›PMID 40967212›Full record

ArticleStructure (London, England : 1993)2025

Molecular basis of DNA recognition by the HMG-box-C1 module of capicua.

Jonathan Webb, Jeremy J M Liew, Andrew D Gnann, Khandan Ilkhani, MacKenzie Patterson, Sayantanee Paul, Marta Forés, Gerardo Jiménez, Alexey Veraksa, Daniel P Dowling

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2025. 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  3. Article
  4. ThebioRxiv : the preprint server for biology · 2024
    Article
  5. Molecular and therapeutic advancements in Capicua (Frontiers in cell and developmental biology · 2024
    Review
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.

Jonathan WebbChemistry Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Jeremy J M LiewChemistry Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Andrew D GnannChemistry Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Khandan IlkhaniBiology Department, University of Massachusetts Boston, Boston, MA 02125, USA.
MacKenzie PattersonChemistry Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Sayantanee PaulBiology Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Marta ForésInstituto de Biología Molecular de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Parc Cientific de Barcelona, 08028 Barcelona, Spain.
Gerardo JiménezInstituto de Biología Molecular de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Parc Cientific de Barcelona, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
Alexey VeraksaBiology Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Daniel P DowlingChemistry Department, University of Massachusetts Boston, Boston, MA 02125, USA. Electronic address: daniel.dowling@umb.edu.

Funding

Mechanisms of signal integration in developmental control of organ size and tissue patterningR01GM141843 · NIGMS · UNIVERSITY OF MASSACHUSETTS BOSTON · PI VERAKSA, ALEXEY · 2021 to 2024
$1.2M
NIGMS NIH HHS R01 GM141843
6 · The paper itself

Abstract

The HMG-box protein capicua (CIC) is a conserved transcriptional repressor with key functions in development and disease. CIC binding of DNA requires both its HMG-box and a separate domain called C1. How these domains cooperate to recognize specific DNA sequences is not known. Here, we report the crystal structure of the human CIC HMG-box and C1 domains complexed with a DNA oligomer containing a consensus octameric binding site. We find that both domains adopt tri-helical structures that pack against opposite sides of the DNA helix. The C1 domain folds into a helix-turn-helix (HTH) structure, inserting into the DNA major groove to enhance affinity. We investigate the system using molecular dynamics simulations and binding assays that interrogate the observed HMG-box and C1 domain interface and prominent cancer variants. Our results reveal a unique bipartite DNA-binding module and provide insights into the effects of cancer and domain interface mutations.

Indexed as

DNARepressor ProteinsBinding SitesCrystallography, X-RayHMG-Box DomainsHumansMolecular Dynamics SimulationMutationNucleic Acid ConformationProtein BindingProtein DomainsDNARepressor Proteinscancer mutationsCICDNA binding affinityEMSAhelix-turn-helixHTHMSTprotein-DNA complexrepressor proteinXray crystallography

Identifiers

PMID40967212
PMCPMC13152641

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.