Plos iconPlosSep 18, 2026 ~1 min source read

Domain classification of archaeal proteomes reveals conserved fold repertoire

To characterize the 21% of proteins lacking high-confidence classification, we applied successive filters for structure prediction confidence, protein length, and structural cluster context, reducing 8,452 domain-free proteins to a small number of well-folded structural orphans (less than 0.1% of the dataset). Archaeal proteins span 987 of the 2,457 ECOD X-groups defined across all cellular life, roughly 40% of known fold diversity captured within a single domain of life.

Domain classification of archaeal proteomes reveals conserved fold repertoire

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Archaeal proteins span 987 of the 2,457 ECOD X-groups defined across all cellular life, roughly 40% of known fold diversity captured within a single domain of life.

To characterize the 21% of proteins lacking high-confidence classification, we applied successive filters for structure prediction confidence, protein length, and structural cluster context, reducing 8,452...

Clustering by Foldseek recovered structural relationships for 63% of domains that are singletons by sequence comparison.

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The useful part

Archaeal proteins span 987 of the 2,457 ECOD X-groups defined across all cellular life, roughly 40% of known fold diversity captured within a single domain of life. Clustering by Foldseek recovered structural relationships for 63% of domains that are singletons by sequence comparison. Dustin Schaeffer, Jimin Pei, Rui Guo, Jing Zhang, Kirill Medvedev, Qian Cong, Nick Grishin Archaea represent one of the three domains of cellular life and yet account for fewer than 1% of experimentally determined protein structures, leaving the extent of their structural novelty unknown.

How it works

  • To characterize the 21% of proteins lacking high-confidence classification, we applied successive filters for structure prediction confidence, protein length, and structural cluster context, reducing 8,452...
  • The unclassified fraction is dominated by sub-threshold matches (matches below the 0.85 DPAM confidence cutoff for high-confidence T-group assignment) to known folds (14% of all proteins) and low-confidence...

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Dustin Schaeffer, Jimin Pei, Rui Guo, Jing Zhang, Kirill Medvedev, Qian Cong, Nick Grishin Archaea represent one of the three domains of cellular life and yet account for fewer than 1% of experimentally determined protein structures, leaving the extent of their structural novelty unknown.

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