Gamete fusion is a critical event of mammalian fertilization. A random one-bead one-compound combinatorial peptide library represented synthetic human egg mimics and identified a previously unidentified ligand as Fc receptor-like 3, named MAIA after the mythological goddess intertwined with JUNO. This immunoglobulin super family receptor was expressed on human oolemma and played a major role during sperm-egg adhesion and fusion. MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. The complexity of the MAIA isotype may offer a cryptic sexual selection mechanism to avoid genetic incompatibility and achieve favorable fitness outcomes.

Centre for Stem Cell Biology University of Sheffield Sheffield S10 2TN UK

Department of Biochemistry and Molecular Medicine University of California Davis School of Medicine Davis CA USA

Department of Cell Biology and Human Anatomy University of California Davis School of Medicine Davis CA USA

Department of Computational and Systems Biology University of Pittsburgh Pittsburgh PA USA

Department of Histology and Embryology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Human Genetics University of Utah Salt Lake City UT USA

Department of Oncology and Metabolism University of Sheffield Medical School Sheffield S10 2RX UK

Department of Veterinary Sciences Faculty of Agrobiology Food and Natural Resources Czech University of Life Sciences Prague Kamycka 129 165 00 Prague Czech Republic

Department of Zoology Faculty of Science Charles University Vinicna 7 128 44 Prague Czech Republic

Imaging Methods Core Facility at BIOCEV Faculty of Science Charles University Prumyslova 595 252 50 Vestec Czech Republic

Laboratory of Molecular Therapy Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Prumyslova 595 252 50 Vestec Czech Republic

Laboratory of Reproductive Biology Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Prumyslova 595 252 50 Vestec Czech Republic

Laboratory of Structural Bioinformatics of Proteins Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Prumyslova 595 252 50 Vestec Czech Republic

ProCrea Swiss IVF Center Prague Czech Republic

Reprofit International Clinic of Reproductive Medicine Brno Czech Republic

Research Institute for Microbial Diseases Osaka University Osaka Japan

School of Pharmacy and Medical Science Griffith University Parklands Avenue Southport Qld 4222 Australia

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Juno and CD9 protein network organization in oolemma of mouse oocyte

Fertilization, but Not Post-Implantation Development, Can Occur in the Absence of Sperm and Oocyte Beta1 Integrin in Mice