LUD, a new protein domain associated with lactate utilization

Area of Science:

• Structural Biology
• Microbiology
• Biochemistry

Background:

• A novel conserved protein domain, DUF162, is present in LutB and LutC proteins, encoded by the LutABC operon involved in bacterial lactate utilization.
• Analysis of sequence, structure, and experimental data supports redefining DUF162 as the LUD (Lactate Utilization Domain) domain family.

Purpose of the Study:

• To redefine the DUF162 protein domain as the LUD domain family based on comprehensive analysis.
• To elucidate the structural and functional characteristics of the LUD domain, including substrate binding and regulation.
• To investigate the significance of LUD-containing proteins in the human gut microbiome and their potential role in Deinococcus radiodurans radiation resistance.

Main Methods:

• Sequence and structural analysis of DUF162-containing proteins.
• Determination of the first crystal structure of a LUD domain protein (LutC from Deinococcus radiodurans) [PDB:2G40].
• Bioinformatic analysis of LUD domain abundance in the human gut microbiome.

Main Results:

• The DUF162 domain is redefined as the LUD domain family.
• The crystal structure of LutC, a LUD domain protein from Deinococcus radiodurans, was solved, revealing similarities to the ISOCOT superfamily.
• LUD domains exhibit increased abundance in the human gut microbiome.

Conclusions:

• A model for substrate and cofactor binding and regulation within the LUD domain is proposed.
• The study highlights the importance of LUD-containing proteins in the human gut microbiome.
• The findings suggest a potential link between lactate metabolism mediated by LUD domains and the radiation resistance of Deinococcus radiodurans.