Abstract Protein structure serves as a critical bridge between sequence and functional annotation, particularly in establishing functional links among distantly homologous proteins with low sequence similarities. However, systematic protein structure-based functional annotations have been lacking in plants, where functions for a significant portion of the proteomes are still elusive. In this study, we leveraged protein structural data from 17 angiosperms to uncover previously unannotated protein functions in plants. After structural clustering, we used the plant clusters to query the UniProtKB/Swiss-Prot database (the expertly curated component of UniProtKB), a repository of expertly curated and reliably annotated proteins, and identified structural matches for thousands of plant clusters that were undetectable by sequence-based BLAST searches. We further selected 120 clusters, which are highly reliable in structural quality and alignment and are well-conserved across plant species, and uncovered various protein functions that are potentially widely important in plants. Finally, we experimentally analyzed one plant cluster structurally resembling the yeast peroxisomal peroxin 8 (PEX8) protein and verified that plant PEX8-like proteins can functionally complement yeast pex8 mutants. Our findings highlight the power of structural comparison in uncovering protein functions in plants.
Chen et al. (2026) studied this question.