Tracing the birth of structural domains from loops during protein evolution
Abstract The structures and functions of proteins are embedded into the loop scaffolds of structural domains. Their origin and evolution remain mysterious. Here, we use a novel graph-theoretical approach to describe how modular and non-modular loop prototypes combine to form folded structures in pro...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-41556-w |
| _version_ | 1827711435747098624 |
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| author | M. Fayez Aziz Fizza Mughal Gustavo Caetano-Anollés |
| author_facet | M. Fayez Aziz Fizza Mughal Gustavo Caetano-Anollés |
| author_sort | M. Fayez Aziz |
| collection | DOAJ |
| description | Abstract The structures and functions of proteins are embedded into the loop scaffolds of structural domains. Their origin and evolution remain mysterious. Here, we use a novel graph-theoretical approach to describe how modular and non-modular loop prototypes combine to form folded structures in protein domain evolution. Phylogenomic data-driven chronologies reoriented a bipartite network of loops and domains (and its projections) into ‘waterfalls’ depicting an evolving ‘elementary functionome’ (EF). Two primordial waves of functional innovation involving founder ‘p-loop’ and ‘winged-helix’ domains were accompanied by an ongoing emergence and reuse of structural and functional novelty. Metabolic pathways expanded before translation functionalities. A dual hourglass recruitment pattern transferred scale-free properties from loop to domain components of the EF network in generative cycles of hierarchical modularity. Modeling the evolutionary emergence of the oldest P-loop and winged-helix domains with AlphFold2 uncovered rapid convergence towards folded structure, suggesting that a folding vocabulary exists in loops for protein fold repurposing and design. |
| first_indexed | 2024-03-10T17:55:39Z |
| format | Article |
| id | doaj.art-211d9ce37a8d49bb918f751dce00ce01 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:55:39Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-211d9ce37a8d49bb918f751dce00ce012023-11-20T09:12:37ZengNature PortfolioScientific Reports2045-23222023-09-0113112110.1038/s41598-023-41556-wTracing the birth of structural domains from loops during protein evolutionM. Fayez Aziz0Fizza Mughal1Gustavo Caetano-Anollés2Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of IllinoisEvolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of IllinoisEvolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of IllinoisAbstract The structures and functions of proteins are embedded into the loop scaffolds of structural domains. Their origin and evolution remain mysterious. Here, we use a novel graph-theoretical approach to describe how modular and non-modular loop prototypes combine to form folded structures in protein domain evolution. Phylogenomic data-driven chronologies reoriented a bipartite network of loops and domains (and its projections) into ‘waterfalls’ depicting an evolving ‘elementary functionome’ (EF). Two primordial waves of functional innovation involving founder ‘p-loop’ and ‘winged-helix’ domains were accompanied by an ongoing emergence and reuse of structural and functional novelty. Metabolic pathways expanded before translation functionalities. A dual hourglass recruitment pattern transferred scale-free properties from loop to domain components of the EF network in generative cycles of hierarchical modularity. Modeling the evolutionary emergence of the oldest P-loop and winged-helix domains with AlphFold2 uncovered rapid convergence towards folded structure, suggesting that a folding vocabulary exists in loops for protein fold repurposing and design.https://doi.org/10.1038/s41598-023-41556-w |
| spellingShingle | M. Fayez Aziz Fizza Mughal Gustavo Caetano-Anollés Tracing the birth of structural domains from loops during protein evolution Scientific Reports |
| title | Tracing the birth of structural domains from loops during protein evolution |
| title_full | Tracing the birth of structural domains from loops during protein evolution |
| title_fullStr | Tracing the birth of structural domains from loops during protein evolution |
| title_full_unstemmed | Tracing the birth of structural domains from loops during protein evolution |
| title_short | Tracing the birth of structural domains from loops during protein evolution |
| title_sort | tracing the birth of structural domains from loops during protein evolution |
| url | https://doi.org/10.1038/s41598-023-41556-w |
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