Journal of Glycobiology
Open Access

O-glycosylation and protein evolution: The case of the LHβ to CGβ development

Glycobiology World Congress

August 10-12, 2015 Philadelphia, USA

David Ben-Menahem

Scientific Tracks Abstracts: J Glycobiol

Abstract :

The glycoprotein hormones LH, FSH and CG are non-covalent heterodimers composed of the common α and hormone
specific β 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 CGβ 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 α, LHβ and FSHβ subunits are generic to vertebrates, the CGβ gene is restricted to primates and equids.
This is curious because the CGβ gene presumably evolved from the ancestral LHβ 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 1. The potential of the LHβ to CGβ transformation is present in several animal phyla and 2. The ability of a CTP
domain to have the clustered O-glycans is important for the CGβ development. Additional studies with the equine CTPextended
β subunit suggest that this subunit, which is expressed in both in the pituitary and placenta of equids integrates
intracellular properties that diverged in the LHβ and CGβ subunits of primates that are expressed in different tissues. Our
studies demonstrate a potential role for the CTP O-glycosylation in the LHβ to CGβ evolution and a link between tissue
expression and subunit characteristics.

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.