Structure of mitochondrial transcription termination factor 3 reveals a novel nucleic acid-binding domain

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• Mitochondrial transcription termination factors (MTERFs) are vital for regulating gene expression in mammalian cells.
• The MTERF-domain, approximately 270 amino acids long, is conserved across MTERF proteins and is essential for DNA binding and transcription regulation.
• The three-dimensional structure of this conserved MTERF-domain has remained undetermined.

Purpose of the Study:

• To elucidate the structural characteristics of the MTERF-domain.
• To understand the molecular basis of DNA binding and transcription regulation by MTERFs.

Main Methods:

• X-ray crystallography or Cryo-EM to determine the structure of the human MTERF3 MTERF-domain.
• Bioinformatic analysis to identify conserved structural motifs and evolutionary conservation.

Main Results:

• The MTERF-domain of human MTERF3 adopts a half-doughnut-shaped, right-handed superhelix structure.
• This superhelix is composed of alpha-helical tandem repeats forming a novel triangular three-helix motif, termed the MTERF-motif.
• A positively charged nucleic acid-binding path exists on the concave side, indicative of a half clamp binding mode.

Conclusions:

• The MTERF-motif is a conserved structural element across diverse eukaryotic organisms.
• The determined structure provides insights into the mechanism of mitochondrial transcription termination.
• The findings suggest a novel half clamp nucleic acid-binding mode for MTERF-domains.