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Published on: December 20, 2013
AlphaFold-driven structural proteomics reveals extensive cellulosome machinery in human ruminococcal symbionts
Christine Minor1,2, Allen Takayesu1,2, Mark A Arbing2,3
1Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
Cellulosomes, enzyme complexes for breaking down plant matter, are more common and diverse in the human gut than previously thought. Structural analysis revealed new Ruminococcus species and cellulosome types, highlighting their importance in the gut microbiome.
Area of Science:
- Microbiology
- Structural Biology
- Bioinformatics
Background:
- Cellulosomes are crucial for degrading plant polysaccharides but were considered rare in the human gut.
- Sequence-based methods often fail to detect diverse cellulosome-producing bacteria due to sequence divergence.
Purpose of the Study:
- To investigate the prevalence and diversity of cellulosomes in human gut Ruminococcus species.
- To leverage structural proteomics to identify novel cellulosome architectures and producers.
Main Methods:
- Proteome-scale AlphaFold2 structural predictions were used to identify putative cellulosome-producing Ruminococcus species.
- Structure-based clustering was employed to analyze novel cohesin families and cellulosome architectures.
- Experimental validation was combined with computational predictions.
Main Results:
- A significantly expanded set of Ruminococcus species, including previously unrecognized symbionts, were identified as putative cellulosome producers.
- Novel cohesin families with conserved folds despite sequence divergence were discovered, defining distinct cellulosome architectures.
- Ruminococcus species possess elaborate cellulosomes, some invisible to sequence-based annotation, and others enriched in starch-degrading enzymes.
Conclusions:
- Ruminococcal cellulosomes are more prevalent and diverse in the human gut than previously understood.
- Structural proteomics is a powerful tool for uncovering deeply divergent functional systems like cellulosomes.
- These findings redefine the distribution and evolution of cellulosomes in gut microbes and their role in dietary substrate degradation.
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