Glycobiology World Congress

Biography

Biography: Miki Hara-Yokoyama

Abstract

Many proteins have their functions on the cell membranes or organelle membranes. To understand the function on the membranes, it is important to elucidate the cell-surface assembly. The leukocyte cell-surface antigen CD38 is a type II transmembrane glycoprotein and has four N-glycosylation sites. CD38 is the major NAD+ glycohydrolase in mammals, and its ectoenzyme activity is involved in calcium mobilization. CD38 also acts as a lipid raft-dependent signaling molecule to promote cell proliferation or death. CD38 forms a tetramer on the cell surface, but the structural basis and the functional significance of tetramerization have remained unexplored. We identified the interfaces contributing to the homophilic interaction of mouse CD38, by site-specific crosslinking on the cell surface with an expanded genetic code, based on a crystallographic analysis. A combination of the three interfaces enables CD38 to tetramerize: one interface involving the juxtamembrane -helix is responsible for the formation of the core dimer, which is further dimerized via the other two interfaces. This dimerization of dimers underlies the catalytic activity and the localization of CD38 in lipid rafts. The N-linked glycosylation sites are found to be located in strategic positions to prevent further self-association of the tetramer. Accordingly, the glycosylation is likely to ensure the function of CD38, by regulating the cell-surface assembly.