Tetrameric interaction of the ectoenzyme CD38 on the cell surface enables its catalytic and raft-association activities |
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Authors: | Miki Hara-Yokoyama Mutsuko Kukimoto-Niino Kazue Terasawa Satoru Harumiya Katarzyna A Podyma-Inoue Nobumasa Hino Kensaku Sakamoto Satsuki Itoh Noritaka Hashii Yoko Hiruta Nana Kawasaki Chiemi Mishima-Tsumagari Yoko Kaitsu Tomoko Matsumoto Motoaki Wakiyama Mikako Shirouzu Takeshi Kasama Hiroshi Takayanagi Naoko Utsunomiya-Tate Kiyoshi Takatsu Toshiaki Katada Yoshio Hirabayashi Shigeyuki Yokoyama Masaki Yanagishita |
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Affiliation: | Section of Biochemistry, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; The Global Center of Excellence (GCOE) Program, International Research Center for Molecular Sciences in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo 113-8549, Japan. |
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Abstract: | The leukocyte cell-surface antigen CD38 is the major nicotinamide adenide dinucleotide glycohydrolase in mammals, and its ectoenzyme activity is involved in calcium mobilization. CD38 is also a raft-dependent signaling molecule. 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 α-helix is responsible for the formation of the core dimer, which is further dimerized via the other two interfaces. This dimerization of dimers is required for the catalytic activity and the localization of CD38 in membrane rafts. The glycosylation prevents further self-association of the tetramer. Accordingly, the tetrameric interaction underlies the multifaceted actions of CD38. |
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