Crystal Structures of Human CD38 in Complex with NAADP and ADPRP

Mobilization of intracellular Ca²⁺ stores is a critical process for many cell activities. Nicotinic acid adenine dinu- cleotide phosphate (NAADP) is a novel second messenger that can mobilize acidic calcium stores, such as the endo-lysosomes. It is thus functionally distinct from the two other Ca²⁺ signaling messengers, cyclic ADP-ribose and inositol trisphosphate, which target the Ca²⁺ stores in the endoplasmic reticulum. Human CD38, a multifunc- tional protein having both receptor and enzymatic roles in almost all cell types, has been shown to catalyze both the synthesis and degradation of NAADP. Here, we present the first image of this novel messenger in complex with human CD38 as captured by X-ray crystallography. The results provide insight into the degradation mechanism of NAADP by human CD38.