A conserved fertilization complex bridges sperm and egg in vertebrates

Victoria E. Deneke; Andreas Blaha; Yonggang Lu; Johannes P. Suwita; Jonne M. Draper; Clara S. Phan; Karin Panser; Alexander Schleiffer; Laurine Jacob; Theresa Humer; Karel Stejskal; Gabriela Krssakova; Elisabeth Roitinger; Dominik Handler; Maki Kamoshita; Tyler D.R. Vance; Xinyin Wang; Joachim M. Surm; Yehu Moran; Jeffrey E. Lee; Masahito Ikawa; Andrea Pauli

doi:10.1016/j.cell.2024.09.035

A conserved fertilization complex bridges sperm and egg in vertebrates

Victoria E. Deneke^*, Andreas Blaha, Yonggang Lu, Johannes P. Suwita, Jonne M. Draper, Clara S. Phan, Karin Panser, Alexander Schleiffer, Laurine Jacob, Theresa Humer, Karel Stejskal, Gabriela Krssakova, Elisabeth Roitinger, Dominik Handler, Maki Kamoshita, Tyler D.R. Vance, Xinyin Wang, Joachim M. Surm, Yehu Moran, Jeffrey E. LeeMasahito Ikawa, Andrea Pauli^*

^*Corresponding author for this work

Department of Ecology, Evolution & Behavior (EEB)

Research output: Contribution to journal › Article › peer-review

Abstract

Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6. We demonstrate that Tmem81 is essential for male fertility in zebrafish and mice. In line with trimer formation, we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact in vitro. Notably, complex formation creates the binding site for the egg fertilization factor Bouncer in zebrafish. Together, our work presents a comprehensive model for fertilization across vertebrates, where a conserved sperm complex binds to divergent egg proteins—Bouncer in fish and JUNO in mammals—to mediate sperm-egg interaction.

Original language	English
Journal	Cell
DOIs	https://doi.org/10.1016/j.cell.2024.09.035
State	Accepted/In press - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Keywords

AlphaFold
gamete adhesion
male fertility
protein-protein interaction
sperm proteome
sperm-egg interaction
vertebrate fertilization
zebrafish

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10.1016/j.cell.2024.09.035

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Deneke, V. E., Blaha, A., Lu, Y., Suwita, J. P., Draper, J. M., Phan, C. S., Panser, K., Schleiffer, A., Jacob, L., Humer, T., Stejskal, K., Krssakova, G., Roitinger, E., Handler, D., Kamoshita, M., Vance, T. D. R., Wang, X., Surm, J. M., Moran, Y., ... Pauli, A. (Accepted/In press). A conserved fertilization complex bridges sperm and egg in vertebrates. Cell. https://doi.org/10.1016/j.cell.2024.09.035

@article{4a543944652142eaaaa235066f88ebc7,

title = "A conserved fertilization complex bridges sperm and egg in vertebrates",

abstract = "Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6. We demonstrate that Tmem81 is essential for male fertility in zebrafish and mice. In line with trimer formation, we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact in vitro. Notably, complex formation creates the binding site for the egg fertilization factor Bouncer in zebrafish. Together, our work presents a comprehensive model for fertilization across vertebrates, where a conserved sperm complex binds to divergent egg proteins—Bouncer in fish and JUNO in mammals—to mediate sperm-egg interaction.",

keywords = "AlphaFold, gamete adhesion, male fertility, protein-protein interaction, sperm proteome, sperm-egg interaction, vertebrate fertilization, zebrafish",

author = "Deneke, {Victoria E.} and Andreas Blaha and Yonggang Lu and Suwita, {Johannes P.} and Draper, {Jonne M.} and Phan, {Clara S.} and Karin Panser and Alexander Schleiffer and Laurine Jacob and Theresa Humer and Karel Stejskal and Gabriela Krssakova and Elisabeth Roitinger and Dominik Handler and Maki Kamoshita and Vance, {Tyler D.R.} and Xinyin Wang and Surm, {Joachim M.} and Yehu Moran and Lee, {Jeffrey E.} and Masahito Ikawa and Andrea Pauli",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

doi = "10.1016/j.cell.2024.09.035",

language = "אנגלית",

journal = "Cell",

issn = "0092-8674",

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Deneke, VE, Blaha, A, Lu, Y, Suwita, JP, Draper, JM, Phan, CS, Panser, K, Schleiffer, A, Jacob, L, Humer, T, Stejskal, K, Krssakova, G, Roitinger, E, Handler, D, Kamoshita, M, Vance, TDR, Wang, X, Surm, JM, Moran, Y, Lee, JE, Ikawa, M & Pauli, A 2024, 'A conserved fertilization complex bridges sperm and egg in vertebrates', Cell. https://doi.org/10.1016/j.cell.2024.09.035

TY - JOUR

T1 - A conserved fertilization complex bridges sperm and egg in vertebrates

AU - Deneke, Victoria E.

AU - Blaha, Andreas

AU - Lu, Yonggang

AU - Suwita, Johannes P.

AU - Draper, Jonne M.

AU - Phan, Clara S.

AU - Panser, Karin

AU - Schleiffer, Alexander

AU - Jacob, Laurine

AU - Humer, Theresa

AU - Stejskal, Karel

AU - Krssakova, Gabriela

AU - Roitinger, Elisabeth

AU - Handler, Dominik

AU - Kamoshita, Maki

AU - Vance, Tyler D.R.

AU - Wang, Xinyin

AU - Surm, Joachim M.

AU - Moran, Yehu

AU - Lee, Jeffrey E.

AU - Ikawa, Masahito

AU - Pauli, Andrea

PY - 2024

Y1 - 2024

N2 - Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6. We demonstrate that Tmem81 is essential for male fertility in zebrafish and mice. In line with trimer formation, we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact in vitro. Notably, complex formation creates the binding site for the egg fertilization factor Bouncer in zebrafish. Together, our work presents a comprehensive model for fertilization across vertebrates, where a conserved sperm complex binds to divergent egg proteins—Bouncer in fish and JUNO in mammals—to mediate sperm-egg interaction.

AB - Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6. We demonstrate that Tmem81 is essential for male fertility in zebrafish and mice. In line with trimer formation, we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact in vitro. Notably, complex formation creates the binding site for the egg fertilization factor Bouncer in zebrafish. Together, our work presents a comprehensive model for fertilization across vertebrates, where a conserved sperm complex binds to divergent egg proteins—Bouncer in fish and JUNO in mammals—to mediate sperm-egg interaction.

KW - AlphaFold

KW - gamete adhesion

KW - male fertility

KW - protein-protein interaction

KW - sperm proteome

KW - sperm-egg interaction

KW - vertebrate fertilization

KW - zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85207814260&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2024.09.035

DO - 10.1016/j.cell.2024.09.035

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 39423812

AN - SCOPUS:85207814260

SN - 0092-8674

JO - Cell

JF - Cell

ER -

A conserved fertilization complex bridges sperm and egg in vertebrates

Abstract

Bibliographical note

Keywords

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