Ben-Gurion University of the Negev, Israel
David Ben-Menahem has completed his PhD at Tel-Aviv University in Tel-Aviv Israel, and did his postdoctorate studies at Washington University Medical School, in St. Louis Missouri, USA. He is at the department of Clinical Biochemistry and Pharmacology at Ben-Gurion University of the Negev in Beer-Sheva, Israel. His major research focus is related to structure-function studies of the gonadotropins which are members of the glycoprotein hormone family.
The glycoprotein hormones LH, FSH and CG are non-covalent heterodimers composed of the common and hormone specific 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 CG 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 , LH and FSH subunits are generic to vertebrates, the CG gene is restricted to primates and equids. This is curious because the CG gene presumably evolved from the ancestral LH 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 LH to CG 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 CG development. Additional studies with the equine CTP-extended subunit suggest that this subunit, which is expressed in both in the pituitary and placenta of equids integrates intracellular properties that diverged in the LH and CG subunits of primates that are expressed in different tissues. Our studies demonstrate a potential role for the CTP O-glycosylation in the LH to CG evolution, and a link between tissue expression and subunit characteristics.
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