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Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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General Transcription Factors01:30

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Transcription Factors02:16

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Restarting Stalled Replication Forks02:37

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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Spreading of Chromatin Modifications

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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
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Related Experiment Video

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Investigating Protein-protein Interactions in Live Cells Using Bioluminescence Resonance Energy Transfer
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FoxP3 forkhead dimer: Don't swap me now.

Indra Bekere1, Carina C de Oliveira Mann1

  • 1Institute of Virology, Technical University of Munich, 81675 Munich, Germany.

Immunity
|August 10, 2022
PubMed
Summary

FoxP3 protein is essential for immune balance. New research shows its head-to-head conformation enables specific DNA binding and specialized regulatory T cell functions.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Forkhead box P3 (FoxP3) is a crucial transcription factor for regulatory T cell (Treg) development and function.
  • Immune homeostasis relies heavily on the proper functioning of Tregs, which suppress excessive immune responses.
  • Dysregulation of FoxP3 function is linked to various autoimmune diseases and immune disorders.

Purpose of the Study:

  • To elucidate the structural mechanisms by which FoxP3 recognizes specific DNA sequences.
  • To understand how FoxP3 achieves functional specialization within regulatory T cells.
  • To provide insights into the molecular basis of immune homeostasis regulated by FoxP3.

Main Methods:

  • X-ray crystallography was employed to determine the three-dimensional structure of FoxP3.

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  • Biochemical assays were used to assess the DNA-binding properties of FoxP3 in different conformations.
  • Cellular assays were performed to evaluate the functional impact of FoxP3 conformation on Treg activity.

    • Main Results:

    • FoxP3 adopts a unique head-to-head domain conformation.
    • This specific conformation is critical for high-affinity and sequence-specific binding to target DNA elements.
    • The structural conformation directly influences FoxP3's ability to mediate Treg-specific gene expression and function.

    Conclusions:

    • The head-to-head domain conformation of FoxP3 is a key determinant of its DNA recognition specificity.
    • This structural insight explains how FoxP3 achieves functional specialization in regulatory T cells.
    • Understanding FoxP3's structural dynamics offers potential therapeutic targets for immune-related diseases.