ArticleCurrent biology : CB2017
Structure-Function Studies Link Class II Viral Fusogens with the Ancestral Gamete Fusion Protein HAP2.
Article in Current biology : CB, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 126 citations in OpenAlex.
- Molecular determinants of species-specific gamete adhesion triggering HAP2-mediated membrane fusion.Nature communications · 2026Article
- The SPARK complex forms the molecular basis of vertebrate fertilization.bioRxiv : the preprint server for biology · 2026Article
- Crystal structure and nanobodies against domain 3 of the malaria parasite fusogen Plasmodium falciparum HAP2.The Biochemical journal · 2026Article
- Sulfur-containing class of broad-spectrum antivirals improves influenza virus vaccine development.Nature communications · 2026Article
- A Genome-Wide Modeling and Characterization Study of Pleckstrin Homology Domains inPlants (Basel, Switzerland) · 2025Article
- Fusogenic Nanoreactor-Based Detection of Extracellular Vesicle-derived miRNAs for Diagnosing Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- The Role of Membrane-Bound Extracellular Vesicles During Co-Stimulation and Conjugation in the CiliateMicroorganisms · 2025Article
- Structural and antigenic characterization of Babesia Bovis HAP2 domains.Scientific reports · 2025Article
- Novel requirements for HAP2/GCS1-mediated gamete fusion iniScience · 2024Article
- Cip1, a CDK regulator, determines heterothallic mating or homothallic selfing in a protist.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Vaccination of cattle with the Babesia bovis sexual-stage protein HAP2 abrogates parasite transmission by Rhipicephalus microplus ticks.NPJ vaccines · 2023Article
- The EGF-motif-containing protein SPE-36 is a secreted sperm protein required for fertilization in C. elegans.Current biology : CB · 2023Article
- A Frame-by-Frame Glance at Membrane Fusion Mechanisms: From Viral Infections to Fertilization.Biomolecules · 2023Review
- Divergent molecular signatures in fish Bouncer proteins define cross-fertilization boundaries.Nature communications · 2023Article
- A novel function for the sperm adhesion protein IZUMO1 in cell-cell fusion.The Journal of cell biology · 2023Article
- Behavior of Male Gamete Fusogen GCS1/HAP2 and the Regulation inBiomolecules · 2023Article
- B-cell epitope discovery: The first protein flexibility-based algorithm-Zika virus conserved epitope demonstration.PloS one · 2023Article
- Cellular and Natural Viral Engineering in Cognition-Based Evolution.Communicative & integrative biology · 2023Review
- Eukaryotic fertilization and gamete fusion at a glance.Journal of cell science · 2022Article
- DMP8 and 9 regulate HAP2/GCS1 trafficking for the timely acquisition of sperm fusion competence.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The conserved transmembrane protein, HAP2/GCS1, has been linked to fertility in a wide range of taxa and is hypothesized to be an ancient gamete fusogen. Using template-based structural homology modeling, we now show that the ectodomain of HAP2 orthologs from Tetrahymena thermophila and other species adopt a protein fold remarkably similar to the dengue virus E glycoprotein and related class II viral fusogens. To test the functional significance of this predicted structure, we developed a flow-cytometry-based assay that measures cytosolic exchange across the conjugation junction to rapidly probe the effects of HAP2 mutations in the Tetrahymena system. Using this assay, alterations to a region in and around a predicted "fusion loop" in T. thermophila HAP2 were found to abrogate membrane pore formation in mating cells. Consistent with this, a synthetic peptide corresponding to the HAP2 fusion loop was found to interact directly with model membranes in a variety of biophysical assays. These results raise interesting questions regarding the evolutionary relationships of class II membrane fusogens and harken back to a long-held argument that eukaryotic sex arose as the byproduct of selection for the horizontal transfer of a "selfish" genetic element from cell to cell via membrane fusion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.