Researchers at the Swedish medical university Karolinska Institutet have been able to describe the 3D structure of a complete egg receptor that binds sperm at the beginning of fertilization. The results, published in the journal Cell, will lead to better understanding of infertility and may enable entirely new types of contraceptives.
For centuries, the imagination of people has been grasped by the encounter of gametes -- egg and sperm-, whose union gives rise to a new individual. At the beginning of conception, sperm binds to proteins in the extracellular coat of the egg, called zona pellucida (ZP). But the molecular details of this fundamental biological event have so far remained obscure.
Luca Jovine's research team at Karolinska Institutet has now managed to determine the three-dimensional structure of the receptor molecule that binds sperm, called ZP3. The detailed structural information, based on data collected at the European Synchrotron Radiation Facility (ESRF), makes it possible to begin exploring at the molecular level how the egg interacts with sperm at fertilization.
The study suggests which parts of the receptor are likely to be directly contacted by sperm, and provides new insights into how the sperm receptor is assembled and secreted from the egg. The findings have important implications for human reproductive medicine, as they may explain how mutations in the sperm receptor gene could cause infertility. The research could also potentially lead to the design of non-hormonal contraceptives specifically targeting egg-sperm interaction.
"The results give a remarkable picture of the female side of fertilization," says Luca Jovine, who has led the study. "But this is, of course, only half of the story. The next step will be to tackle the corresponding molecules on sperm that allow it to bind to the egg."
The research was performed in collaboration with Prof. Tsukasa Matsuda at Nagoya University, Japan, and Dr. David Flot at the ESRF. It was funded by the Center for Biosciences; the Swedish Research Council; the EU Sixth Framework Programme; the Scandinavia-Japan Sasakawa Foundation; Grant-in-aids from the Japan Society for the Promotion of Science and MEXT; and an EMBO Young Investigator award to Luca Jovine.
- Ling Han, Magnus Monnι, Hiroki Okumura, Thomas Schwend, Amy L. Cherry, David Flot, Tsukasa Matsuda, Luca Jovine. Insights into Egg Coat Assembly and Egg-Sperm Interaction from the X-Ray Structure of Full-Length ZP3. Cell, 2010; DOI: 10.1016/j.cell.2010.09.041
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