Insights into Egg Coat Assembly and Egg-Sperm Interaction from the X-Ray Structure of Full-Length ZP3

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.09.041 Byline: Ling Han (1), Magnus Monne (1), Hiroki Okumura (1)(2), Thomas Schwend (1), Amy L. Cherry (1), David Flot (3), Tsukasa Matsuda (4), Luca Jovine (1) Keywords: CELLBIO; HUMDISEASE Abstract: ZP3, a major component of the zona pellucida (ZP) matrix coating mammalian eggs, is essential for fertilization by acting as sperm receptor. By retaining a propeptide that contains a polymerization-blocking external hydrophobic patch (EHP), we determined the crystal structure of an avian homolog of ZP3 at 2.0 A resolution. The structure unveils the fold of a complete ZP domain module in a homodimeric arrangement required for secretion and reveals how EHP prevents premature incorporation of ZP3 into the ZP. This suggests mechanisms underlying polymerization and how local structural differences, reflected by alternative disulfide patterns, control the specificity of ZP subunit interaction. Close relative positioning of a conserved O-glycan important for sperm binding and the hypervariable, positively selected C-terminal region of ZP3 suggests a concerted role in the regulation of species-restricted gamete recognition. Alternative conformations of the area around the O-glycan indicate how sperm binding could trigger downstream events via intramolecular signaling. Author Affiliation: (1) Department of Biosciences and Nutrition and Center for Biosciences, Karolinska Institutet, Halsovagen 7, Huddinge SE-141 83, Sweden (2) Department of Applied Biological Chemistry, Faculty of Agriculture, Meijo University, 1-501 Shiogamaguchi, Tempaku-ku, Nagoya 468-8502, Japan (3) EMBL Grenoble, 6 Rue Jules Horowitz, BP 181, 38042 Grenoble Cedex 9, France (4) Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan Article History: Received 23 June 2010; Revised 11 August 2010; Accepted 24 August 2010 Article Note: (miscellaneous) Published online: October 21, 2010