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David Ben-Menahem

David Ben-Menahem

Ben-Gurion University of the Negev, Israel

Title: O-glycosylation and protein evolution: the case of the LH to CG development

Biography

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.

Abstract

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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