Crystal structure of human CD38 extracellular domain.
Human CD38 is a multifunctional protein involved in diverse functions. As an enzyme, it is responsible for the synthesis of two Ca2+ messengers, cADPR and NAADP; as an antigen, it is involved in regulating cell adhesion, differentiation, and proliferation. Besides, CD38 is a marker of progression of HIV-1 infection and a negative prognostic marker of B-CLL. We have determined the crystal structure of the soluble extracellular domain of human CD38 to 1.9 A resolution. The enzyme's overall topology is similar to the related proteins CD157 and the Aplysia ADP-ribosyl cyclase, except with large structural changes at the two termini. The extended positively charged N terminus has lateral associations with the other CD38 molecule in the crystallographic asymmetric unit. The analysis of the CD38 substrate binding models revealed two key residues that may be critical in controlling CD38's multifunctionality of NAD hydrolysis, ADP-ribosyl cyclase, and cADPR hydrolysis activities.
Liu
Qun
Q
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Kriksunov
Irina A
IA
Graeff
Richard
R
Munshi
Cyrus
C
Lee
Hon Cheung
HC
Hao
Quan
Q
D036541:ADP-ribosyl Cyclase / Q000737:chemistry / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1 / Q000737:chemistry*; D000595:Amino Acid Sequence; D002384:Catalysis; D003461:Crystallography; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D019143:Evolution, Molecular; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D006868:Hydrolysis; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1