Tetrameric interaction of the ectoenzyme CD38 on the cell surface enables its catalytic and raft-association activities

Structure. 2012 Sep 5;20(9):1585-95. doi: 10.1016/j.str.2012.06.017. Epub 2012 Aug 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / chemistry*
  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Cell Line
  • Chromatography, Gel
  • Cross-Linking Reagents / chemistry
  • Crystallography, X-Ray
  • Cystine / chemistry
  • Glycosylation
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Lipids / metabolism
  • Membrane Microdomains / metabolism*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Interaction Domains and Motifs
  • Protein Multimerization*
  • Protein Processing, Post-Translational
  • Protein Stability
  • Protein Structure, Quaternary


  • Cross-Linking Reagents
  • Membrane Glycoproteins
  • Membrane Lipids
  • Cystine
  • Cd38 protein, mouse
  • ADP-ribosyl Cyclase 1