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 (see press photos). 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.
Publication: "Insights into Egg Coat Assembly and Egg-Sperm Interaction from the X-Ray Structure of Full-Length ZP3", Ling Han, Magnus Monné, Hiroki Okumura, Thomas Schwend, Amy L. Cherry, David Flot, Tsukasa Matsuda & Luca Jovine, Cell, 21 October 2010.
Download images: http://ki.se/pressroom
For further information, please contact:
Dr Luca Jovine
Center for Biosciences
Department of Biosciences and Nutrition
Tel: +46 (0)8-608 33 01
Mobile: +46 (0)70-149 70 14
Lab web page: Jovinelab.org
Press Officer Katarina Sternudd
Tel: +46 (0)8-524 838 95
Karolinska Institutet is one of the world's leading medical universities. Its mission is to contribute to the improvement of human health through research and education. Karolinska Institutet accounts for over 40 per cent of the medical academic research conducted in Sweden, and offers the country's broadest range of education in medicine and health sciences. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine. More information on http://ki.se.
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