Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA
Abstract MoeA, also known as gephyrin in higher eukaryotes, is an enzyme essential for molybdenum cofactor (Moco) biosynthesis and involved in GABA and GlyR receptor clustering at the synapse in animals. We recently discovered that Actinobacteria have a repurposed version of MoeA (Glp) linked to bac...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07476-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594468661886976 |
|---|---|
| author | Daniela Megrian Mariano Martinez Pedro M. Alzari Anne Marie Wehenkel |
| author_facet | Daniela Megrian Mariano Martinez Pedro M. Alzari Anne Marie Wehenkel |
| author_sort | Daniela Megrian |
| collection | DOAJ |
| description | Abstract MoeA, also known as gephyrin in higher eukaryotes, is an enzyme essential for molybdenum cofactor (Moco) biosynthesis and involved in GABA and GlyR receptor clustering at the synapse in animals. We recently discovered that Actinobacteria have a repurposed version of MoeA (Glp) linked to bacterial cell division. Since MoeA exists in all domains of life, our study explores how it gained multifunctionality over time. We use phylogenetic inference and protein structure analyses to study its diversity and evolutionary history. Glp-expressing Bacteria have at least two copies of the gene, and analysis of their putative active sites suggests that Glp lost its enzymatic role. In Archaea, we find an ancestral duplication, with one paralog that may bind tungsten instead of molybdenum. Early eukaryotes acquired MoeA from Bacteria, MogA fused with MoeA in the opisthokont ancestors, and it finally gained roles in anchoring inhibitory neurotransmitters. Our findings highlight MoeA’s functional versatility and repurposing. |
| format | Article |
| id | doaj-art-32c7c13c94ed4985b751362e0bc5f0df |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-32c7c13c94ed4985b751362e0bc5f0df2025-01-19T12:35:32ZengNature PortfolioCommunications Biology2399-36422025-01-018111210.1038/s42003-025-07476-3Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeADaniela Megrian0Mariano Martinez1Pedro M. Alzari2Anne Marie Wehenkel3Institut Pasteur, CNRS UMR 3528, Université Paris Cité, Structural Microbiology UnitInstitut Pasteur, CNRS UMR 3528, Université Paris Cité, Structural Microbiology UnitInstitut Pasteur, CNRS UMR 3528, Université Paris Cité, Structural Microbiology UnitInstitut Pasteur, CNRS UMR 3528, Université Paris Cité, Structural Microbiology UnitAbstract MoeA, also known as gephyrin in higher eukaryotes, is an enzyme essential for molybdenum cofactor (Moco) biosynthesis and involved in GABA and GlyR receptor clustering at the synapse in animals. We recently discovered that Actinobacteria have a repurposed version of MoeA (Glp) linked to bacterial cell division. Since MoeA exists in all domains of life, our study explores how it gained multifunctionality over time. We use phylogenetic inference and protein structure analyses to study its diversity and evolutionary history. Glp-expressing Bacteria have at least two copies of the gene, and analysis of their putative active sites suggests that Glp lost its enzymatic role. In Archaea, we find an ancestral duplication, with one paralog that may bind tungsten instead of molybdenum. Early eukaryotes acquired MoeA from Bacteria, MogA fused with MoeA in the opisthokont ancestors, and it finally gained roles in anchoring inhibitory neurotransmitters. Our findings highlight MoeA’s functional versatility and repurposing.https://doi.org/10.1038/s42003-025-07476-3 |
| spellingShingle | Daniela Megrian Mariano Martinez Pedro M. Alzari Anne Marie Wehenkel Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA Communications Biology |
| title | Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA |
| title_full | Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA |
| title_fullStr | Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA |
| title_full_unstemmed | Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA |
| title_short | Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA |
| title_sort | evolutionary plasticity and functional repurposing of the essential metabolic enzyme moea |
| url | https://doi.org/10.1038/s42003-025-07476-3 |
| work_keys_str_mv | AT danielamegrian evolutionaryplasticityandfunctionalrepurposingoftheessentialmetabolicenzymemoea AT marianomartinez evolutionaryplasticityandfunctionalrepurposingoftheessentialmetabolicenzymemoea AT pedromalzari evolutionaryplasticityandfunctionalrepurposingoftheessentialmetabolicenzymemoea AT annemariewehenkel evolutionaryplasticityandfunctionalrepurposingoftheessentialmetabolicenzymemoea |