This region of the ZP3 polypeptide also includes 4 conserved Cys residues in close proximity to one another (mZP3, Cys-320, −322, −323, and −328 hZP3, Cys-319, −321, −322, and −327) that could form two intramolecular disulfides. Notably, mZP1 and 2 and hZP1, 2, and 4 have only 3 to 5 aa between the ZPD and the CFCS ( red), whereas mZP3 has 47 aa and hZP3 has 45 aa between the ZPD and the CFCS which includes the sperm combining-site and represents a region of positive Darwinian selection during evolution. mZP3 (424 aa) and hZP3 (424 aa) are the smallest of the ZP proteins and consist primarily of a ZPD (mZP3 260 aa hZP3 259 aa). mZP1, hZP1, and hZP4 have one additional ZP-N subdomain (N1 green) between the N-terminus of the polypeptide and the TD. mZP2 (713 aa) and hZP2 (745 aa) have 3 additional ZP-N subdomains (N1-N3 green) between the N-terminus of the polypeptide and the ZPD. mZP1 (623 aa), hZP1 (638 aa), and hZP4 (540 aa) also have a trefoil domain (TD brown) adjacent to the ZPD. In each case, the polypeptide has a signal sequence (SS magenta) at the N-terminus a ZP domain (ZPD) consisting of two subdomains, ZP-N ( green) and ZP-C ( cyan), and a C-terminal propeptide (CTP). Linker region ( blue) concensus furin cleavage-site (CFCS arrow) transmembrane domain (TMD yellow) and cytoplasmic tail ( black) in the C-terminus. Schematic representation of the organization of mouse (m) zona pellucida (ZP) proteins mZP1–3 and human (h) ZP proteins hZP1–4. ZP domain ZP genes ZP proteins gene sequence variations gene targeting human human fertility mouse mouse fertility oogenesis zona pellucida. These findings are discussed in light of our current knowledge of ZP protein synthesis, processing, secretion, and assembly. Results of a large number of studies of infertile female patients strongly suggest that gene sequence variations (GSV) in human ZP1, ZP2, or ZP3 due to point, missense, or frameshift mutations have similar deleterious effects on ZP formation and female fertility. Female mice with eggs that lack a ZP due to inactivation of either ZP2 or ZP3 are completely infertile, whereas inactivation of ZP1 results in construction of an abnormal ZP and reduced fertility. Inactivation of mouse ZP1, ZP2, or ZP3 by gene targeting affects both ZP formation around oocytes and fertility. The fibrils are cross-linked by ZP1 to form a thick, transparent ECM to which sperm must first bind and then penetrate during fertilization of eggs. Secreted ZP proteins assemble into long fibrils around growing oocytes with ZP2-ZP3 dimers located periodically along the fibrils. All ZP proteins have a zona pellucida domain (ZPD) that consists of ≈270 amino acids and has 8 conserved Cys residues present as four intramolecular disulfides. The mouse and human ZP is composed of three or four unique proteins, respectively, called ZP1-4, that are synthesized, processed, and secreted by oocytes during their growth phase. The zona pellucida (ZP) is an extracellular matrix (ECM) that surrounds all mammalian oocytes, eggs, and embryos and plays vital roles during oogenesis, fertilization, and preimplantation development.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |