Interactions between mouse ZP2 glycoprotein and proacrosin; a mechanism for secondary binding of sperm to the zona pellucida during fertilization.
The mouse zona pellucida glycoprotein, mZP2, is thought to be the secondary receptor on eggs for retention of acrosome-reacted sperm during fertilization. Here, we present evidence that one of its complementary binding proteins on sperm is proacrosin/acrosin. mZP2 binds to proacrosin null sperm considerably less effectively than to wild-type sperm. Binding is mediated by a strong ionic interaction between polysulphate groups on mZP2 and basic residues on an internal proacrosin peptide. The stereochemistry of both sulphate groups and basic amino acids determines the specificity of binding. Structurally relevant sulphated polymers and suramin, a polysulphonated anticancer drug, compete with mZP2 for complementary binding sites on proacrosin/acrosin in solid-phase binding assays. The same competitors also displace attached sperm from the zona pellucida of eggs in an in vitro fertilization system. This combination of genetic, biochemical and functional data supports the hypothesis that mZP2-proacrosin interactions are important for retention of acrosome-reacted sperm on the egg surface during fertilization. Safe mimetics of suramin have potential as non-steroidal antifertility agents.
Howes
E
E
Signalling Programme, The Babraham Institute, Cambridge CB2 4AT, UK.
Pascall
J C
JC
Engel
W
W
Jones
R
R
D000176:Acrosin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004527:Egg Proteins / Q000378:metabolism*; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005306:Fertilization / Q000502:physiology*; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D015394:Molecular Structure; D010063:Ovum / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*; D015044:Zona Pellucida / Q000737:chemistry / Q000378:metabolism*; D000072216:Zona Pellucida Glycoproteins
D000970:Antineoplastic Agents; D004527:Egg Proteins; D004792:Enzyme Precursors; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D013431:Sulfates; D000072216:Zona Pellucida Glycoproteins; C000606520:Zp2 protein, mouse; D013498:Suramin; C022438:proacrosin; D000176:Acrosin