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Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex.

Aydin H, Sultana A, Li S, Thavalingam A, Lee JE
Nature 534 562-5 (2016)
Related entries: 5f4q, 5f4t, 5f4v

Cited: 66 times
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Abstract

Fertilization is an essential biological process in sexual reproduction and comprises a series of molecular interactions between the sperm and egg. The fusion of the haploid spermatozoon and oocyte is the culminating event in mammalian fertilization, enabling the creation of a new, genetically distinct diploid organism. The merger of two gametes is achieved through a two-step mechanism in which the sperm protein IZUMO1 on the equatorial segment of the acrosome-reacted sperm recognizes its receptor, JUNO, on the egg surface. This recognition is followed by the fusion of the two plasma membranes. IZUMO1 and JUNO proteins are indispensable for fertilization, as constitutive knockdown of either protein results in mice that are healthy but infertile. Despite their central importance in reproductive medicine, the molecular architectures of these proteins and the details of their functional roles in fertilization are not known. Here we present the crystal structures of human IZUMO1 and JUNO in unbound and bound conformations. The human IZUMO1 structure exhibits a distinct boomerang shape and provides structural insights into the IZUMO family of proteins. Human IZUMO1 forms a high-affinity complex with JUNO and undergoes a major conformational change within its N-terminal domain upon binding to the egg-surface receptor. Our results provide insights into the molecular basis of sperm-egg recognition, cross-species fertilization, and the barrier to polyspermy, thereby promising benefits for the rational development of non-hormonal contraceptives and fertility treatments for humans and other mammals.

Reviews - 5f4e mentioned but not cited (1)

  1. The cell biology of fertilization: Gamete attachment and fusion. Siu KK, Serrão VHB, Ziyyat A, Lee JE. J Cell Biol 220 e202102146 (2021)

Articles - 5f4e mentioned but not cited (5)

  1. Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex. Aydin H, Sultana A, Li S, Thavalingam A, Lee JE. Nature 534 562-565 (2016)
  2. SPACA6 ectodomain structure reveals a conserved superfamily of gamete fusion-associated proteins. Vance TDR, Yip P, Jiménez E, Li S, Gawol D, Byrnes J, Usón I, Ziyyat A, Lee JE. Commun Biol 5 984 (2022)
  3. In silico Docking Analysis for Blocking JUNO-IZUMO1 Interaction Identifies Two Small Molecules that Block in vitro Fertilization. Stepanenko N, Wolk O, Bianchi E, Wright GJ, Schachter-Safrai N, Makedonski K, Ouro A, Ben-Meir A, Buganim Y, Goldblum A. Front Cell Dev Biol 10 824629 (2022)
  4. Juno and CD9 protein network organization in oolemma of mouse oocyte. Frolikova M, Sur VP, Novotny I, Blazikova M, Vondrakova J, Simonik O, Ded L, Valaskova E, Koptasikova L, Benda A, Postlerova P, Horvath O, Komrskova K. Front Cell Dev Biol 11 1110681 (2023)
  5. Molecular dynamics of JUNO-IZUMO1 complexation suggests biologically relevant mechanisms in fertilization. Pacak P, Kluger C, Vogel V. Sci Rep 13 20342 (2023)


Reviews citing this publication (21)

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