Three-dimensional structure of the zona pellucida.
The zona pellucida is the extracellular coat that surrounds the mammalian oocyte. It forms a spherical shell of remarkably uniform thickness (5-10 microns in eutherian mammals). The mouse is currently the largest source of data on the zona pellucida and this review is built largely on these data. The zona pellucida is composed of three proteins in both mice and humans: ZP1, ZP2 and ZP3. These proteins are glycosylated and, in mice, have mature relative molecular masses of 200,000, 120,000 and 83,000, respectively. ZP1 is a dimer of two apparently identical subunits. All three mouse proteins have been sequenced and possess transmembrane domains at their C-terminal ends coupled with furin cleavage sites immediately upstream. Sequence data have been used to provide an accurate assessment of the mole ratios of the three proteins. The ratio of ZP2:ZP3 is close to 1:1, whereas ZP1 is approximately 9% of the combined mole amounts of ZP2 and ZP3. Ultrastructural evidence suggests that the mouse zona pellucida is composed of filaments constructed by head-to-tail association of globular proteins. The coordinate synthesis of the three zona pellucida proteins coupled with the near 1:1 stoichiometry of ZP2 and ZP3 is consistent with a model in which ZP2-ZP3 heterodimers are the basic repeating units of the filament, with cross-linking of filaments by dimeric ZP1. This model is also consistent with data from ZP2 and ZP3 gene knockout and antisense experiments. However, the structure remains unproven. The small amount of ZP1 relative to ZP2 and ZP3 may have important implications for the distribution of ZP1 cross-links, since the number of cross-linking sites potentially exceeds the number of ZP1 dimer molecules by a considerable margin. The evidence that ZP1, ZP2 and ZP3 are all synthesized via a membrane-bound step is discussed and two models are proposed for the assembly of the zona pellucida. The cortical reaction and its effect on the zona pellucida are examined in detail. It is shown that the amount of material released by cortical granules could be of the order of 30% by mass of ZP1, and that if this material was distributed predominantly on the inner face of the zona pellucida, its local concentration could approach that of ZP1. A model in which the zona block to polyspermy is caused by direct titration of zona pellucida binding sites is suggested as an alternative to the explanation that relies on enzyme cleavage of ZP2 to ZP2f. Finally, some of the major experimental and structural issues that remain to be addressed are identified.
Green
D P
DP
Department of Anatomy and Structural Biology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand.
D000818:Animals; D004527:Egg Proteins / Q000032:analysis / Q000737:chemistry*; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry*; D051379:Mice; D011487:Protein Conformation; D011956:Receptors, Cell Surface; D015044:Zona Pellucida / Q000737:chemistry* / Q000502:physiology; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C000606514:ZP1 protein, human; C000606515:ZP2 protein, human; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606519:Zp1 protein, mouse; C000606520:Zp2 protein, mouse; C000606521:Zp3 protein, mouse