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Structure determination of the zona pellucida domain by X-ray crystallography

Objective

For all sexually reproducing organisms fertilisation is a fundamental step to ensure the continuity of the species. The events that take place during fertilisation are poorly understood at the molecular level, although a number of components that play crucial roles in this process have been identified in mammals. The mammalian oocyte is surrounded by the zona pellucida (ZP), a specialised extra-cellular matrix consisting of filaments of polymerised ZP domain proteins. Some of these ZP domain proteins serve a s species-specific receptors for the initial recognition of sperm. Upon fusion of the gametes, modification of ZP subunits leads to morphological changes of the whole matrix that inactivate its receptor activity as part of the block against the entry of additional sperm.

The goal of this project is to determine the first three-dimensional structure of a ZP domain. So far, no structure is available for this conserved protein, which is thought to adopt a unique fold. Solving the structure would be of outmost importance for understanding the molecular mechanism of crucial steps of fertilisation. Since more than one hundred extra-cellular proteins with diverse functions contain ZP domains, a structure would have implications far beyond the field of fertilisation and it would allow detailed interpretation of the effect of the many ZP domain mutations that cause disease in humans.

Call for proposal

FP6-2004-MOBILITY-11
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Funding Scheme

ERG - Marie Curie actions-European Re-integration Grants

Coordinator

KAROLINSKA INSTITUTET
Address
Nobels Vag 5
Stockholm
Sweden