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 ZP3gene.[1] ZP3 is the receptor in the zona pellucida which binds sperm at the beginning of fertilization.
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.[1]
3D Structure
X-ray crystallographic studies of the N-terminal half of mammalian ZP3 (PDB: 3D4C, 3D4G, 3EF7)[2] as well as its full-length avian homolog (PDB: 3NK3, 3NK4)[3] 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.[3]
↑Monné M, Han L, Schwend T, Burendahl S, Jovine L (2008). "Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats". Nature. 456 (7222): 653–7. doi:10.1038/nature07599. PMID19052627. PDB: 3D4C, 3D4G, 3EF7
↑ 3.03.1Han L, Monné M, Okumura H, Schwend T, Cherry AL, Flot D, Matsuda T, Jovine L (2010). "Insights into egg coat assembly and egg-sperm interaction from the X-ray structure of full-length ZP3". Cell. 143 (3): 404–15. doi:10.1016/j.cell.2010.09.041. PMID20970175. PDB: 3NK3, 3NK4
Further reading
Bansal P, Chakrabarti K, Gupta SK (2009). "Functional activity of human ZP3 primary sperm receptor resides toward its C-terminus". Biol. Reprod. 81 (1): 7–15. doi:10.1095/biolreprod.108.074716. PMID19246320.
Bleil JD, Wassarman PM (1980). "Mammalian sperm-egg interaction: identification of a glycoprotein in mouse egg zonae pellucidae possessing receptor activity for sperm". Cell. 20 (3): 873–82. doi:10.1016/0092-8674(80)90334-7. PMID7418009.
Caballero-Campo P, Chirinos M, Fan XJ, et al. (2006). "Biological effects of recombinant human zona pellucida proteins on sperm function". Biol. Reprod. 74 (4): 760–8. doi:10.1095/biolreprod.105.047522. PMID16407501.
Chiu PC, Wong BS, Chung MK, et al. (2008). "Effects of native human zona pellucida glycoproteins 3 and 4 on acrosome reaction and zona pellucida binding of human spermatozoa". Biol. Reprod. 79 (5): 869–77. doi:10.1095/biolreprod.108.069344. PMID18667750.
Choudhury S, Ganguly A, Chakrabarti K, et al. (2009). "DNA vaccine encoding chimeric protein encompassing epitopes of human ZP3 and ZP4: immunogenicity and characterization of antibodies". J. Reprod. Immunol. 79 (2): 137–47. doi:10.1016/j.jri.2008.09.002. PMID19004505.
Florman HM, Wassarman PM (1985). "O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity". Cell. 41 (1): 313–24. doi:10.1016/0092-8674(85)90084-4. PMID2986849.
Furlong LI, Harris JD, Vazquez-Levin MH (2005). "Binding of recombinant human proacrosin/acrosin to zona pellucida (ZP) glycoproteins. I. Studies with recombinant human ZPA, ZPB, and ZPC". Fertil. Steril. 83 (6): 1780–90. doi:10.1016/j.fertnstert.2004.12.042. PMID15950651.
Gook DA, Edgar DH, Borg J, Martic M (2008). "Detection of zona pellucida proteins during human folliculogenesis". Hum. Reprod. 23 (2): 394–402. doi:10.1093/humrep/dem373. PMID18033806.
Han L, Monné M, Okumura H, Schwend T, Cherry AL, Flot D, Matsuda T, Jovine L (2010). "Insights into egg coat assembly and egg-sperm interaction from the X-ray structure of full-length ZP3". Cell. 143 (3): 404–15. doi:10.1016/j.cell.2010.09.041. PMID20970175. PDB: 3NK3 PDB: 3NK4
Jovine L, Qi H, Williams Z, Litscher E, Wassarman PM (2002). "The ZP domain is a conserved module for polymerization of extracellular proteins". Nat. Cell Biol. 4 (6): 457–61. doi:10.1038/ncb802. PMID12021773.
Monné M, Han L, Schwend T, Burendahl S, Jovine L (2008). "Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats". Nature. 456 (7222): 653–7. doi:10.1038/nature07599. PMID19052627. PDB: 3D4C PDB: 3D4G PDB: 3EF7
Ni Y, Li K, Xu W, et al. (2007). "Acrosome reaction induced by recombinant human zona pellucida 3 peptides rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 and their mechanism". J. Androl. 28 (3): 381–8. doi:10.2164/jandrol.106.001289. PMID17192598.
Rankin T, Dean J (2000). "The zona pellucida: using molecular genetics to study the mammalian egg coat". Rev. Reprod. 5 (2): 114–21. doi:10.1530/ror.0.0050114. PMID10864856.
Törmälä RM, Jääskeläinen M, Lakkakorpi J, et al. (2008). "Zona pellucida components are present in human fetal ovary before follicle formation". Mol. Cell. Endocrinol. 289 (1–2): 10–5. doi:10.1016/j.mce.2008.01.029. PMID18502569.
van Duin M, Polman JE, Verkoelen CC, Bunschoten H, Meyerink JH, Olijve W, Aitken RJ (December 1992). "Cloning and characterization of the human sperm receptor ligand ZP3: evidence for a second polymorphic allele with a different frequency in the Caucasian and Japanese populations". Genomics. 14 (4): 1064–70. doi:10.1016/S0888-7543(05)80130-2. PMID1478648.
Wassarman PM, Jovine L, Litscher ES (2001). "A profile of fertilization in mammals". Nat. Cell Biol. 3 (2): E59–64. doi:10.1038/35055178. PMID11175768.
Zhao M, Boja ES, Hoodbhoy T, et al. (2004). "Mass spectrometry analysis of recombinant human ZP3 expressed in glycosylation-deficient CHO cells". Biochemistry. 43 (38): 12090–104. doi:10.1021/bi048958k. PMID15379548.
