IspH-RPS1 and IspH-UbiA: "Rosetta Stone" Proteins

Area of Science:

• Biochemistry
• Molecular Biology
• Microbiology

Background:

• The protein IspH is essential for isoprenoid biosynthesis via the methylerythritol phosphate pathway.
• IspH contains a vital 4Fe-4S cluster for its catalytic activity.

Purpose of the Study:

• To investigate the diversity and function of IspH proteins using sequence similarity networks.
• To characterize novel IspH protein fusions, specifically IspH-RPS1 and IspH-UbiA.

Main Methods:

• Sequence similarity network analysis to identify IspH protein families.
• Biochemical characterization of IspH-RPS1 fusion proteins and mutants.

Main Results:

• Identified over 400 IspH proteins, many fused to ribosomal protein S1 (RPS1) or UbiA-like proteins, often twice the size of previously studied IspHs.
• IspH-RPS1 fusions are prevalent in human gut anaerobes and pathogens; IspH-UbiA fusions are found in sulfate-reducing anaerobes.
• Elimination of RPS1 domains did not affect IspH catalytic activity, suggesting they are not essential for catalysis.

Conclusions:

• First isolation of catalytically active IspH-RPS1 and identification of IspH-UbiA hybrids.
• These fusion proteins may be functionally linked to isoprenoid production and UbiA-like prenyl transferase activity.
• IspH-RPS1 hybrids might play roles in bacterial stringent response or act as Fe/O2 sensors.