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Panorama of ancient metazoan macromolecular complexes

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ABSTRACT

Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we then generated a draft conservation map consisting of >1 million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering revealed a spectrum of conservation, ranging from ancient Eukaryal assemblies likely serving cellular housekeeping roles for at least 1 billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, by affinity-purification and by functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic significance and adaptive value to animal cell systems.

No MeSH data available.


Distribution of uncharacterized proteins and novel interactions across the 981 derived complexesComplexes were sorted by median age (defined by OMA). Among 2,153 unique proteins, 293 (red) lack Gene Ontology (GO) functional annotations, while 1,756 of 7,665 co-complex interactions are novel (light green) (i.e., not listed in iRef curation database).
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Figure 13: Distribution of uncharacterized proteins and novel interactions across the 981 derived complexesComplexes were sorted by median age (defined by OMA). Among 2,153 unique proteins, 293 (red) lack Gene Ontology (GO) functional annotations, while 1,756 of 7,665 co-complex interactions are novel (light green) (i.e., not listed in iRef curation database).

Mentions: We also observed broad agreement between the derived complexes’ inferred molecular weights (assuming 1:1 stiochiometries) and migration by size exclusion chromatography (Fig. 4c; Extended Data Fig. 7a) and density gradient centrifugation (Extended Data Fig. 7b). A prime example is the coherent profiles of a large (~500 kDa) ‘mixed’ complex with several unannotated components (Fig. 4d; Extended Data Fig. 8), dubbed Commander because most subunits share COMM (copper metabolism MURR1) domains30 implicated in copper toxicosis31, among other roles30,32. Commander contains coiled-coil domain proteins CCDC22 and CCDC93 (Figs. 4a, d) in addition to ten COMM domain proteins, broadly supported by co-fractionation in human, fly and sea urchin (Extended Data Fig. 9a–c and Supporting Web Site).


Panorama of ancient metazoan macromolecular complexes
Distribution of uncharacterized proteins and novel interactions across the 981 derived complexesComplexes were sorted by median age (defined by OMA). Among 2,153 unique proteins, 293 (red) lack Gene Ontology (GO) functional annotations, while 1,756 of 7,665 co-complex interactions are novel (light green) (i.e., not listed in iRef curation database).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036527&req=5

Figure 13: Distribution of uncharacterized proteins and novel interactions across the 981 derived complexesComplexes were sorted by median age (defined by OMA). Among 2,153 unique proteins, 293 (red) lack Gene Ontology (GO) functional annotations, while 1,756 of 7,665 co-complex interactions are novel (light green) (i.e., not listed in iRef curation database).
Mentions: We also observed broad agreement between the derived complexes’ inferred molecular weights (assuming 1:1 stiochiometries) and migration by size exclusion chromatography (Fig. 4c; Extended Data Fig. 7a) and density gradient centrifugation (Extended Data Fig. 7b). A prime example is the coherent profiles of a large (~500 kDa) ‘mixed’ complex with several unannotated components (Fig. 4d; Extended Data Fig. 8), dubbed Commander because most subunits share COMM (copper metabolism MURR1) domains30 implicated in copper toxicosis31, among other roles30,32. Commander contains coiled-coil domain proteins CCDC22 and CCDC93 (Figs. 4a, d) in addition to ten COMM domain proteins, broadly supported by co-fractionation in human, fly and sea urchin (Extended Data Fig. 9a–c and Supporting Web Site).

View Article: PubMed Central - PubMed

ABSTRACT

Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we then generated a draft conservation map consisting of >1 million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering revealed a spectrum of conservation, ranging from ancient Eukaryal assemblies likely serving cellular housekeeping roles for at least 1 billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, by affinity-purification and by functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic significance and adaptive value to animal cell systems.

No MeSH data available.