ArticleBMC evolutionary biology2009
Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes.
Article in BMC evolutionary biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 130 citations in OpenAlex.
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- High Molecular Weight Kininogen: A Review of the Structural Literature.International journal of molecular sciences · 2021Review
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- Mialostatin, a Novel Midgut Cystatin fromInternational journal of molecular sciences · 2021Article
- Evolutionary Analysis of Cystatins of Early-Emerging Metazoans Reveals a Novel Subtype in Parasitic Cnidarians.Biology · 2021Article
- Repurposing the McoTI-II Rigid Molecular Scaffold in to Inhibitor of 'Papain Superfamily' Cysteine Proteases.Pharmaceuticals (Basel, Switzerland) · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. Although they have been the subject of many studies, little is known about their genesis, evolution and functional diversification. Our aim has been to obtain a comprehensive insight into their origin, distribution, diversity, evolution and classification in Eukaryota, Bacteria and Archaea.
resultsWe have identified in silico the full complement of the cystatin superfamily in more than 2100 prokaryotic and eukaryotic genomes. The analysis of numerous eukaryotic genomes has provided strong evidence for the emergence of this superfamily in the ancestor of eukaryotes. The progenitor of this superfamily was most probably intracellular and lacked a signal peptide and disulfide bridges, much like the extant Giardia cystatin. A primordial gene duplication produced two ancestral eukaryotic lineages, cystatins and stefins. While stefins remain encoded by a single or a small number of genes throughout the eukaryotes, the cystatins have undergone a more complex and dynamic evolution through numerous gene and domain duplications. In the cystatin superfamily we discovered twenty vertebrate-specific and three angiosperm-specific orthologous families, indicating that functional diversification has occurred only in multicellular eukaryotes. In vertebrate orthologous families, the prevailing trends were loss of the ancestral inhibitory activity and acquisition of novel functions in innate immunity. Bacterial cystatins and stefins may be emergency inhibitors that enable survival of bacteria in the host, defending them from the host's proteolytic activity.
conclusionThis study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification. The findings of this comprehensive study provide guides for future structural and evolutionary studies of the cystatin superfamily as well as of other protease inhibitors and proteases.
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