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bioRxiv · 10.1101/2025.07.11.664487

Mapping the Metalloproteome of Deinococcus indicus DR1 through Integrative Structure and Function Annotation

Ramesh, S. D.·Vasan, G.·Senthilkumar, S.·Thambiraja, M.·Sethi, D.·Priyadarshini, R.·Yennamalli, R. M.
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Abstract

Deinococcus indicus DR1 is a rod-shaped bacterium isolated from the Dadri wetlands (Uttar Pradesh, India) that tolerates ionizing radiation and arsenic. The molecular basis of its wider heavy-metal resilience, particularly among the 1017 out of 4128 proteins still annotated as hypothetical, remains unclear. We performed a proteome-wide structural and functional survey to address this gap. All the 4128 proteins were modeled with AlphaFold2, yielding very-high-confidence structures (pLDDT [≥] 90) for 2145 sequences. CATH/InterPro analysis assigned domains to 2735 proteins. Functions were predicted by combining DeepFRI (graph neural-network), MorphologFinder (Foldseek plus EggNOG-Mapper), and existing GenBank annotations. The integrated workflow suggests that more than 100 previously uncharacterized proteins may bind or transport arsenic, chromium, cobalt, copper, iron, manganese, molybdenum, nickel, or zinc, indicating a metal-handling capacity that extends beyond the known ars operon. Recurrent domain architectures that include P-loop NTPases, Rossmann folds, GNAT acetyl-transferases, and sensor modules (CHASE, PAS, GAF) point to coordinated redox regulation and efflux pathways. Twenty high-confidence metal-binding candidates have been prioritized for experimental validation through expression, mutagenesis, and knockout studies. All structural models, domain assignments, and query tools are available at https://deinococcus.in, providing a resource for future investigations of heavy-metal tolerance in this organism.

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Ramesh, S. D., Vasan, G., Senthilkumar, S., Thambiraja, M., Sethi, D., Priyadarshini, R., Yennamalli, R. M.. 2025-07-17. Mapping the Metalloproteome of Deinococcus indicus DR1 through Integrative Structure and Function Annotation. https://doi.org/10.1101/2025.07.11.664487

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