6GF8

Molecular basis of egg coat filament cross-linking: structure of the glycosylated ZP1 ZP-N1 domain homodimer

Summary for 6GF8

• Entry DOI: 10.2210/pdb6gf8/pdb
• Related: 6GF6 6GF7
• Descriptor: Zona pellucida sperm-binding protein 1,Zona pellucida sperm-binding protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: zona pellucida, zp1, zp-n domain, zp module, zp domain, egg coat filament cross-linking, egg coat penetration by sperm, cell adhesion
• Biological source: Gallus gallus (Chicken); More
• Total number of polymer chains: 2
• Total formula weight: 32438.61

Authors

Nishimura, K.,Jovine, L. (deposition date: 2018-04-29, release date: 2019-06-19, Last modification date: 2024-10-09)

Primary citation

Nishimura, K.,Dioguardi, E.,Nishio, S.,Villa, A.,Han, L.,Matsuda, T.,Jovine, L.
Molecular basis of egg coat cross-linking sheds light on ZP1-associated female infertility.
Nat Commun, 10:3086-3086, 2019

PubMed Abstract: Mammalian fertilisation begins when sperm interacts with the egg zona pellucida (ZP), whose ZP1 subunit is important for fertility by covalently cross-linking ZP filaments into a three-dimensional matrix. Like ZP4, a structurally-related component absent in the mouse, ZP1 is predicted to contain an N-terminal ZP-N domain of unknown function. Here we report a characterisation of ZP1 proteins carrying mutations from infertile patients, which suggests that, in human, filament cross-linking by ZP1 is crucial to form a stable ZP. We map the function of ZP1 to its ZP-N1 domain and determine crystal structures of ZP-N1 homodimers from a chicken homolog of ZP1. These reveal that ZP filament cross-linking is highly plastic and can be modulated by ZP1 fucosylation and, potentially, zinc sparks. Moreover, we show that ZP4 ZP-N1 forms non-covalent homodimers in chicken but not in human. Together, these data identify human ZP1 cross-links as a promising target for non-hormonal contraception.

PubMed: 31300655
DOI: 10.1038/s41467-019-10931-5

Experimental method

X-RAY DIFFRACTION (3.1 Å)