An international team of scientists from the Karolinska Institutet in Sweden and Nagoya University has explained how mutations in egg coat protein ZP1 cause infertility in women. The study suggests that ZP1 could be a promising candidate for future non-hormonal contraceptive efforts.
ZP1 is a glycoprotein involved in the fertilization of eggs by cross-linking egg coat filaments. Because studies in mice showed that lack of ZP1 reduces but does not abolish fertility, scientists believed that this molecule was also not crucial for fertility in humans. This new study, however, suggests that ZP1 may have a much more important role in human reproduction than previously thought. “The results were a big surprise because they suggested that mutations that truncate the human ZP1 protein cause female sterility by hindering its cross-linking function, rather than interfering with other egg coat proteins”, explains Luca Jovine, professor at the Karolinska Institutet and leader of the study.
Image: The mutation W83R of human ZP1 does not hinder its secretion but reduces its cross-linking (panel b), likely due to the fact that – as suggested by the structure of chicken ZP1 (panel a) – W83 (W72 in chicken ZP1) stacks between a sugar attached to ZP1 and the loop that makes the cross-link (“cd loop”). The part of the sugar chain that stacks against W83, which is a fucose residue, was only resolved in the structure of the fully glycosylated protein (violet) whose data came from ESRF ID23-1.