Zona pellucida sperm-binding protein 3, also known as zona pellucida glycoprotein 3 (Zp-3) or the sperm receptor, is a ZP module-containing protein that in humans is encoded by the ZP3 gene.[5] ZP3 is the glycoprotein in the zona pellucida most important for inducting the acrosome reaction of sperm cells at the beginning of fertilization.[6]
The zona pellucida (ZP) is a specialized extracellular matrix that surrounds the oocyte and early embryo. It is composed of three or four glycoproteins (ZP1-4) with various functions during oogenesis, fertilization and preimplantation development. The protein encoded by this gene is a major structural component of the ZP and functions in primary binding and stimulation of the sperm acrosome reaction. The nascent protein contains a N-terminal signal peptide sequence, a conserved "ZP domain" module, a consensus furin cleavage site (CFCS), a polymerization-blocking external hydrophobic patch (EHP), and a C-terminal transmembrane domain. Cleavage at the CFCS separates the mature protein from the EHP, allowing it to incorporate into nascent ZP filaments. A variation in the last exon of this gene has previously served as the basis for an additional ZP3 locus; however, sequence and literature review reveals that there is only one full-length ZP3 locus in the human genome. Another locus encoding a bipartite transcript designated POMZP3 contains a duplication of the last four exons of ZP3, including the above described variation, and maps closely to this gene.[5]
Orthologs of these genes are found throughout Vertebrata. The western clawed frog appears to have two orthologs, and the sea lamprey has seven.[7]
X-ray crystallographic studies of the N-terminal half of mammalian ZP3 (PDB: 3D4C, 3D4G, 3EF7, 5OSQ)[8] as well as its full-length avian homolog (PDB: 3NK3, 3NK4)[9] revealed that the protein's ZP module consists of two immunoglobulin-like domains, ZP-N and ZP-C. The latter, which contains EHP as well as a ZP3-specific subdomain, interacts with the ZP-N domain of a second molecule to generate an antiparallel homodimeric arrangement required for protein secretion.[9]