Extracellular domin of YWK-II, interacts with rat Mullerian-inhibiting substance..pdf

Introduction Sperm membrane proteins probably play an important role in fertilization. A human sperm membrane protein, YWK-II component, has been isolated and characterized, and the coding gene identified (Yan et al., 1990; Huang et al., 2000). The open reading frame consists of 763 codons encoding a polypeptide characteristic of a single trans- membrane protein, established by hydropathicity analysis. The transmembrane and cytoplasmic domains of the YWK- II component and the βA4-amyloid precursor protein (APP) of Alzheimer disease have 70% similarity. The similarity is higher with the amyloid precursor homologues, APPH/ APLP2 (Yan et al., 1990; Sprecher et al., 1993). The YWK-II protein and APP can be delineated into three domains: extracellular, hydrophobic transmembrane and cytoplas- mic. The extracellular domains of these two proteins are distinctly different. Three peptide segments (YAL-198, YAL- 201 and YAL-212) corresponding to a section of the extracellular domain of YWK-II were synthesized as a multiple antigen peptide (MAP) and administered to female rats to assess whether anti-YWK-II antibodies may be a cause of infertility. The YAL-198 induced infertility in seven out of 12 female rats and subfertility in two animals. Sera obtained from infertile rats immunized with YAL-198 contained higher titres of antibodies compared with those obtained from fertile animals, indicating that anti-YWK-II antibodies possess antifertility activity (Vanage et al., 1992). A study of the molecular properties of YWK-II com- ponent revealed that the cytoplasmic domain binds specifically Go, a GTP-binding protein (Huang et al., 2000), indicating that the YWK-II component can couple with G proteins and may activate the signal transduction system of responsive cells. The two-hybrid system relies on the modulating property of eukaryotic site-specific transcrip- tional activators to generate signals after the interaction of a protein fused to a DNA-binding domain with another pro