The three-dimensional structure of the egg protein that binds sperm during fertilisation has finally been determined. The work could lead to a new generation of contraceptives and help to explain how sperm defects cause infertility.
The sperm receptor protein, ZP3, is part of the egg's strong outer coating, called the zona pellucida, and it helps to ensure that – in general – only sperm from the correct species can fertilise the egg. The sequence of amino acids that makes up ZP3 was discovered over 20 years ago, but attempts to work out which parts of the protein are involved in sperm binding have identified several different regions.
Researchers needed the protein's three-dimensional structure to make sense of the results. The standard way to reveal a protein's structure is to fire X-rays at a crystal form of the protein to see how they are deflected, but mammalian versions of ZP3 proved extremely difficult to work with. So Luca Jovine of the Karolinska Institute in Stockholm, Sweden, and colleagues studied the chicken version of the protein instead.
They used X-ray equipment at the European Synchrotron Radiation Facility in Grenoble, France, to determine the structure of chicken ZP3 and then fitted mammalian ZP3 sequences onto that structure with the help of a computer program. "We can make quite a good model of the human protein", says Jovine, although the results are not perfect.
The various components previously implicated in sperm binding seem to sit close together on one surface of the protein. "It reconciles the data coming from different groups," says Jovine.
As well as providing clues to how sperm defects block fertilisation, the findings could lead to a new type of contraceptive. The researchers point out that no novel contraceptive method has been introduced in the past 50 years, since the development of the hormone-based pill.
Working out the shape of the surface involved in sperm binding raises the possibility of designing small molecules to disrupt the process, and so prevent conception, which might have fewer side effects than hormone-based drugs. The researchers now hope to look at the structure of egg-sperm complexes to see how the two sides of the process work together.
Journal reference: Cell, DOI: 10.1016/j.cell.2010.09.041
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