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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
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.
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.
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.