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GAMETE RECOGNITION

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Molecular Basis of Mammalian Egg Sperm Interaction

At the dawn of the 21st century, our knowledge of the molecular mechanism of mammalian fertilization remains very limited. Different lines of evidence indicate that initial gamete recognition depends on interaction between a few d... ver más

31/12/2015

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2015-12-31 No tenemos la información de la convocatoria

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Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto At the dawn of the 21st century, our knowledge of the molecular mechanism of mammalian fertilization remains very limited. Different lines of evidence indicate that initial gamete recognition depends on interaction between a few distinct proteins on sperm and ZP3, a major component of the extracellular coat of oocytes, the zona pellucida (ZP). On the other hand, recent findings suggest an alternative mechanism in which cleavage of another ZP subunit, ZP2, regulates binding of gametes by altering the global structure of the ZP. Progress in the field has been hindered by the paucity and heterogeneity of native egg-sperm recognition proteins, so that novel approaches are needed to reconcile all available data into a single consistent model of fertilization. Following our recent determination of the structure of the most conserved domain of sperm receptor ZP3 by X-ray crystallography, we will conclusively establish the basis of mammalian gamete recognition by performing structural studies of homogeneous, biologically active recombinant proteins. First, we will combine crystallographic studies of isolated ZP subunits with electron microscopy analysis of their filaments to build a structural model of the ZP. Second, structures of key egg-sperm recognition protein complexes will be determined. Third, we will investigate how proteolysis of ZP2 triggers overall conformational changes of the ZP upon gamete fusion. Together with functional analysis of mutant proteins, these studies will provide atomic resolution snapshots of the most crucial step in the beginning of a new life, directly visualizing molecular determinants responsible for species-restricted gamete interaction at fertilization. The progressive decrease of births in the Western world and inadequacy of current contraceptive methods in developing countries underscore an urgent need for a modern approach to reproductive welfare. This research will not only shed light on a truly fundamental biological problem, but also constitute a solid foundation for the reproductive medicine of the future.

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