David Ben-Menahem
Ben-Gurion University of the Negev, Israel
Title: O-glycosylation and protein evolution: the case of the LHï¢ to CGï¢ development
Biography
Biography: David Ben-Menahem
Abstract
The glycoprotein hormones LH, FSH and CG are non-covalent heterodimers composed of the common ï¡ and hormone specific ï¢ subunit. The subunits contain N-linked glycans, which are important for the folding, heterodimer assembly and bioactivity of the hormone. In addition, the carboxy-terminal region of the CGï¢ subunit is O-glycosylated, and this unique domain (known as the CTP) extends the circulatory survival of CG relative to the other glycoprotein hormones. While the genes encoding the ï¡, LHï¢ and FSHï¢ subunits are generic to vertebrates, the CGï¢ gene is restricted to primates and equids. This is curious because the CGï¢ gene presumably evolved from the ancestral LHï¢ gene following only a small set of mutations, and the resulting O-glycosylated CTP confers new hormonal properties to CG relative to LH that seems advantageous to maintain early gestation. To address this restricted evolution, we combined bioinformatics, in-vitro and in-vivo experiments that suggest a) the potential of the LHï¢ to CGï¢ transformation is present in several animal phyla, and b) the ability of a CTP domain to have the clustered O-glycans is important for the CGï¢ development. Additional studies with the equine CTP-extended ï¢ subunit suggest that this subunit, which is expressed in both in the pituitary and placenta of equids integrates intracellular properties that diverged in the LHï¢ and CGï¢ subunits of primates that are expressed in different tissues. Our studies demonstrate a potential role for the CTP O-glycosylation in the LHï¢ to CGï¢ evolution, and a link between tissue expression and subunit characteristics.
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