Helix Unwinding and Base Flipping Enable Human MTERF1 to Terminate Mitochondrial Transcription
Defects in mitochondrial gene expression are associated with aging and disease. Mterf proteins have been implicated in modulating transcription, replication and protein synthesis. We have solved the structure of a member of this family, the human mitochondrial transcriptional terminator MTERF1, bound to dsDNA containing the termination sequence. The structure indicates that upon sequence recognition MTERF1 unwinds the DNA molecule, promoting eversion of three nucleotides. Base flipping is critical for stable binding and transcriptional termination. Additional structural and biochemical results provide insight into the DNA binding mechanism and explain how MTERF1 recognizes its target sequence. Finally, we have demonstrated that the mitochondrial pathogenic G3249A and G3244A mutations interfere with key interactions for sequence recognition, eliminating termination. Our results provide insight into the role of mterf proteins and suggest a link between mitochondrial disease and the regulation of mitochondrial transcription.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 1020213
- Report Number(s):
- BNL--95503-2011-JA
- Journal Information:
- Cell, Journal Name: Cell Journal Issue: 6 Vol. 141; ISSN 0092-8674; ISSN CELLB5
- Country of Publication:
- United States
- Language:
- English
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A minimal motif for sequence recognition by mitochondrial transcription factor A (TFAM)
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Fri Dec 30 23:00:00 EST 2011
· Transcription
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OSTI ID:1042309
A minimal motif for sequence recognition by mitochondrial transcription factor A (TFAM)
Journal Article
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Sun Dec 19 19:00:00 EST 2021
· Nucleic Acids Research
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OSTI ID:1836600