Oocyte receptor JUNO Interactions with IZUMO1 Sperm Membrane

Princess Ferguson '20 and Noah Whipskey '20


I. Introduction

Model View:
Color Scheme:

is an oocyte receptor, plays an imporant role in the fertilization of IZUMO1 , a sperm membrane bound protein. Fertilization is one of the crucial steps in sexual reproduction, the combination of male and female gametes to create life. The fusion of haploid sperm and ooctye is the defining step in mammalian fertilization, which leads to the formation of a diploid organism. A two-step process is needed for the combination of the two gametes; IZUMO1 recognizes the receptor on the egg surface of JUNO . After the egg surface reveals previously concealed receptors, an acrosome reaction take place. The plasma membranes are fused together. After fertilization has occured, the zone pellucida which is a specialized extracellular matrix and oolemma which is a plasmid membrane in the ovum are changed biochemically. This step causes the rejection of any additional incoming, sperm which could potentially create nonviable embryos.

II. General Structure

JUNO contains eight , α 1-8 and four , β 1-4 forming a single globular fold. These core complexes are stabilized by eight disulfide bonds that are conserved among FRs 10,11, riboflavin-binding protein 12, and JUNO . A glycosylphosphatidylinositol-anchored, cysteine-rich glycoprotein receptor (FR) for IZUMO1 that is located on the egg's surface. Due to the folate binding pocket in FRs, there are corresponding hydrophobic interactions.


Model View:
Color Scheme:

and exist in a 1:1 crystal complex, that stabilizes during the gamete fusion process. IZUMO1 , similar to JUNO , contains α helices that are important factors in the adhesion of the sperm. It has three domains, the containing α helices, a region, and the immunoglobulin-like domain. Their interface comprises of IZUMO1 regions of α helices 2 and 3, central β-hairpin regions 1,2,8, and 9, and JUNO α helices 1,2 and 3. The main platform for JUNO binding is the β-hairpin region of IZUMO1 . Crystal structures have shown that residues from all three IZUMO1 domains interact with JUNO through hydrophobic, van der Waals, and aromatic interactions.

When binding to the egg-surface receptor, Human IZUMO1 forms a high-affinity complex with JUNO , causing a confirmational change in the N-terminus and hinge region. The helices of the N-terminal region move about 20Å towards JUNO , and the β-hairpin region shift about 8Å. Causing the formation of IZUMO1 to change from a boomerang shape to an upright position.

IV. Binding with IZUMO1

Fertilization is a fundamental and necessary step in sexual reproduction, that involve the binding of the sperm and egg. This process causes the complex to undergo a confirmational change. Without the fusion of the two, fertilization will not happen and the creation of a genetically distinct dipolid organism will not happen. For the sperm to bind to the egg, there is a two-step mechanism which involves the IZUMO1 protein recognizing the receptor on the egg surface of JUNO . The fusion of two plasma membranes is next.

The final step in fertilization is when the sperm travels to the egg and reaches the the female oviduct, a tube an ovum or egg passes through from the ovary. This involves the sperm breaking through the zona pellucida glycoprotein layer, the plasma membrane, to reach the space between the zona layer and the plasma membrane of the oocyte. The fusion of the sperm and the membrane then allow the formation of the zygote. Subsequently, the fertilized egg quickly sheds the JUNO molecules to neutralize incoming acrosome-reacted sperm, and prevent polyspermy.

V. Mutations

To confirm the structure of IZUMO1 - JUNO binding, studies were conducted to determine what was necessary for binding. The results revealed that the amino acid residues, W62 JUNO and L81 JUNO , are conserved in most mammalian species. Single or multiple mutations in the binding inferace between JUNO and IZUMO1 have been shown to affect the sperm's ability to bind to the egg. Together, the hydrophobic aromatic, van der Waals, and electrostatic interactions stabilize the IZUMO1 - JUNO interface, allowing them to become resilient to mutations.

Although there are conserved sequences, approximately half of the residues vary across mammalian species. These residues include: JUNO
and IZUMO1 :
. These residues are considered to have the same ability to limit the binding of IZUMO1 and JUNO in specific species.

VI. References

Gunasekera, Angelo, Yon W. Ebright, and Richard Ohto, Umeharu, et al. “Structure of IZUMO1–JUNO Reveals Sperm–Oocyte Recognition during Mammalian Fertilization.” Nature News, Nature Publishing Group, 15 June 2016, www.nature.com/articles/nature18596#supplementary-information.

Aydin, Halil, et al. “Molecular Architecture of the Human Sperm IZUMO1 and Egg JUNO Fertilization Complex.” Nature News, Nature Publishing Group, 15 June 2016, www.nature.com/articles/nature18595#f2.

Bianchi, Enrica, et al. “Juno Is the Egg Izumo Receptor and Is Essential for Mammalian Fertilization.” Nature News, Nature Publishing Group, 16 Apr. 2014, www.nature.com/articles/nature13203.

Back to Top

#s/o to Peter Reinhart the real mvp