ArticleCurrent biology : CB2016
Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes.
Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Molecular interplay between sperm and oocyte: a narrative review.Human reproduction update · 2026Review
- Cross-species insemination reveals mouse sperm ability to enter and cross the fish micropyle.eLife · 2025Article
- Molecular mechanisms leading to gamete fusion.Fukushima journal of medical science · 2025Review
- FOLR2Cell communication and signaling : CCS · 2025Review
- Acrosomal Matrix Proteins sp56 and AM67 and Gamete Adhesion in Mammals.Academia biology · 2025Article
- Article
- Dynamic profiles of lncRNAs reveal a functional natural antisense RNA that regulates the development of Schistosoma japonicum.PLoS pathogens · 2024Article
- Molecular dynamics of JUNO-IZUMO1 complexation suggests biologically relevant mechanisms in fertilization.Scientific reports · 2023Article
- MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human fertilization.Science advances · 2022Article
- The Importance of Gene Duplication and Domain Repeat Expansion for the Function and Evolution of Fertilization Proteins.Frontiers in cell and developmental biology · 2022Review
- Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer.Cancers · 2021Review
- Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling.Nature communications · 2021Article
- The cell biology of fertilization: Gamete attachment and fusion.The Journal of cell biology · 2021Review
- The conserved fertility factor SPACA4/Bouncer has divergent modes of action in vertebrate fertilization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Sperm IZUMO1 Is Required for Binding Preceding Fusion With Oolemma in Mice and Rats.Frontiers in cell and developmental biology · 2021Article
- Genetic diversity in the IZUMO1-JUNO protein-receptor pair involved in human reproduction.PloS one · 2021Article
- Oolemma Receptors in Mammalian Molecular Fertilization: Function and New Methods of Study.Frontiers in cell and developmental biology · 2021Review
- Exploiting the folate receptor α in oncology.Nature reviews. Clinical oncology · 2020Review
- Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- New Insights into the Molecular Events of Mammalian Fertilization.Trends in biochemical sciences · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The interaction between egg and sperm is the first necessary step of fertilization in all sexually reproducing organisms. A decade-long search for a protein pair mediating this event in mammals culminated in the identification of the glycosylphosphatidylinositol (GPI)-anchored glycoprotein Juno as the egg plasma membrane receptor of sperm Izumo1 [1,2]. The Juno-Izumo1 interaction was shown to be essential for fertilization since mice lacking either gene exhibit sex-specific sterility, making these proteins promising non-hormonal contraceptive targets [1,3]. No structural information is available on how gamete membranes interact at fertilization, and it is unclear how Juno - which was previously named folate receptor (FR) 4, based on sequence similarity considerations - triggers membrane adhesion by binding Izumo1. Here, we report the crystal structure of Juno and find that the overall fold is similar to that of FRα and FRβ but with significant flexibility within the area that corresponds to the rigid ligand-binding site of these bona fide folate receptors. This explains both the inability of Juno to bind vitamin B9/folic acid [1], and why mutations within the flexible region can either abolish or change the species specificity of this interaction. Furthermore, structural similarity between Juno and the cholesterol-binding Niemann-Pick disease type C1 protein (NPC1) suggests how the modified binding surface of Juno may recognize the helical structure of the amino-terminal domain of Izumo1. As Juno appears to be a mammalian innovation, our study indicates that a key evolutionary event in mammalian reproduction originated from the neofunctionalization of the vitamin B9-binding pocket of an ancestral folate receptor molecule.
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Registered trials
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.