Oocyte receptor JUNO
Interactions with IZUMO1 Sperm Membrane
Princess Ferguson '20 and Noah Whipskey '20
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.
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
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
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.
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.
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,
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,
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