The nuclear pore complex (NPC) serves as the central transport gateway between nucleus and cytoplasm. NPC biogenesis requires the assembly of over 500 proteins culminating in the fusion of the inner and outer nuclear membranes. The mechanism of membrane fusion is unknown. Here, we elucidate how Brl1 and Brr6 mediate membrane fusion in S. cerevisiae. Our data suggest that both proteins form ring-shaped complexes with membrane-remodeling activity. Brl1 localizes to NPC assembly sites via a nuclear export sequence and interacts with Brr6 across the nuclear envelope through conserved hydrophobic loops. Disrupting this interaction blocks fusion and halts NPC assembly. Molecular dynamics simulations suggest that the Brl1-Brr6 complex drives membrane fusion by forming a channel across the bilayers enabling lipid exchange. Phylogenetic analyses and functional experiments in human cells and D. melanogaster establish CLCC1 as the NPC fusogen in metazoans. Together, our results uncover a conserved membrane fusion mechanism in eukaryotes.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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