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Related Experiment Videos

Ion channels formed by transcription factors recognize consensus DNA sequences.

M T Tosteson1, J B Kim, D J Goldstein

  • 1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. magdalena_tosteson@hms.harvard.edu

Biochimica Et Biophysica Acta
|May 9, 2001
PubMed
Summary

Transcription factors (TFs) interact with lipid membranes, forming distinct ion channels. Cognate DNA binding specifically increases channel conductance, revealing TF membrane spanning and DNA accessibility.

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Biochemistry

Background:

  • Transcription factors (TFs) regulate gene transcription by binding DNA.
  • The physical interactions of TFs beyond DNA binding are not fully understood.

Purpose of the Study:

  • To investigate the membrane interaction properties of transcription factors.
  • To determine if TFs can form ion-permeable channels.
  • To explore the functional consequences of DNA binding on TF-membrane interactions.

Main Methods:

  • Incorporation of purified transcription factors into lipid bilayers.
  • Single-channel recording to measure ion conductance.
  • Electrophysiological analysis of TF-membrane channel activity.
  • Perturbation of TF structure and assessment of functional changes.

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Main Results:

  • Several transcription factors were observed to form ion-permeable channels in lipid membranes.
  • Each TF exhibited a unique single-channel conductance, an 'electrical signature'.
  • Addition of cognate double-stranded DNA significantly increased membrane conductance.
  • This DNA-induced increase was observed when DNA was added to the trans-side, suggesting TFs span the membrane.

Conclusions:

  • Transcription factors possess intrinsic membrane-interacting and ion channel-forming capabilities.
  • TF-membrane channel activity is modulated by cognate DNA binding.
  • These findings suggest TFs span cell membranes, with DNA-binding domains accessible from the trans side.