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Fertility |
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| 04 Dec 2008 | Viewed: 59 | |
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Scientists at the Swedish medical university Karolinska Institutet have
determined the first 3D structure of ZP3, a protein essential for the
interaction between the mammalian egg coat and sperm. The findings,
presented in Nature, gives a first glimpse into the molecular
architecture of animal egg coats, with important implications for the
future of human reproductive medicine and the possibility of developing
novel contraceptives.
The beginning of every new life starts
with fertilization, the most crucial step of which is the initial
species-specific recognition between egg and sperm. The receptors for
sperm, proteins ZP3 and ZP2, contain a common sequence that allows them
to form a matrix of filaments, the so-called zona pellucida that
completely surrounds the egg. The Protein Crystallography Unit at
Karolinska Institutet, led by Dr. Luca Jovine, has now determined the
structure of the most conserved part of this building block, the ZP-N
domain.
"ZP3 was identified almost 30 years ago, but obtaining structural
information on this key reproductive protein has been technically
challenging due to its high heterogeneity", says Luca Jovine.
The zona pellucida is essential for natural fertilization in mammals.
The Karolinska Institutet researchers hope that X-ray crystallographic
characterization of a region of ZP3 that is important for its ability
to polymerize could help explaining cases of human infertility, as well
as lead to the development of novel targeted, non-hormonal
contraceptives. The research made on the ZP-N domain has also provided
insights that extend beyond the field of reproduction. Among other
things, an unexpected parallel has been uncovered with molecular
features that are involved in speciation among invertebrates.
Moreover, ZP-N domains are also found in many other extracellular
proteins that are unrelated to fertilization, but play important roles
in human diseases such as non-syndromic deafness, renal and vascular
disorders, and cancer. In the Nature
paper, an example is discussed that shows how the structure of ZP-N can
be used to understand the molecular basis of some of these disorders.
"Mammalian fertilization involves a highly complex series of events.
Our findings pave the way for future investigations into this
fascinating subject by providing a first snapshot of the beginning of
life at atomic resolution", says Luca Jovine.
The research was supported by Karolinska Institutet, the Swedish Research Council and the EU Sixth Framework Programme.
Publication:
'Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats'
Magnus Monné, Ling Han, Thomas Schwend, Sofia Burendahl & Luca Jovine
Nature, 4 December 2008.
Karolinska Institutet is one of the leading medical universities
in Europe. Through research, education and information, Karolinska
Institutet contributes to improving human health. Each year, the Nobel
Assembly at Karolinska Institutet.
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| News Source: Medical News Today |
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