Domain classification of archaeal proteomes reveals conserved fold repertoire.

Archaeal proteomes contain 987 of 2,457 ECOD X-groups, capturing roughly 40% of known fold diversity within a single domain of life across 65 archaeal classes.

• Why it matters: Archaea have fewer than 1% of experimentally determined protein structures, leaving how structurally novel their proteomes are largely unresolved.
• What they did: The study classified 124,075 proteins from 65 archaeal classes using ECOD on AFDB plus newly predicted AlphaFold3 structures, then used Foldseek clustering and filters to resolve 8,452 domain-free proteins.
• The result: Structural relationships were recovered for 63% of sequence-singleton domains, and the unclassified fraction was mainly sub-threshold ECOD matches (14%) and low-confidence predictions (5%), implying conserved fold repertoire.

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