Predicting the metalloproteome of Deinococcus indicus DR1 through integrative structure and function annotation

Area of Science:

• Microbiology and Biochemistry
• Structural Biology
• Bioinformatics and Computational Biology

Background:

• Deinococcus indicus DR1 exhibits tolerance to ionizing radiation and arsenic.
• The molecular mechanisms underlying its broader heavy-metal resilience, especially for hypothetical proteins, are largely unknown.

Purpose of the Study:

• To conduct a proteome-wide structural and functional analysis of Deinococcus indicus DR1 proteins.
• To identify novel proteins involved in heavy-metal tolerance and detoxification.

Main Methods:

• Proteome-wide modeling using AlphaFold2 for all 4128 proteins.
• Domain assignment using CATH and InterPro.
• Functional prediction integrating DeepFRI, MorphologFinder, and GenBank annotations.

Main Results:

• High-confidence structures were obtained for 2145 proteins.
• Over 100 previously uncharacterized proteins were linked to diverse metal-related functions (binding, transport, detoxification) across multiple metals (Cr, Co, Cu, Fe, Mn, Mo, Ni, Zn).
• Identified novel metal-binding proteins and pathways beyond the known arsenic-resistance (ars) gene cluster.

Conclusions:

• Deinococcus indicus DR1 possesses a more extensive repertoire of metal-associated proteins than previously recognized.
• The study provides a valuable resource of structural models and functional predictions for future experimental validation.
• Identified 20 high-confidence metal-binding candidates for experimental characterization.