Crystal structure of human CD38 extracellular domain

Qun Liu, Irina A. Kriksunov, Richard Graeff, Cyrus Munshi, Cheung Lee Hon, Quan Hao

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

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 Å 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.

Original languageEnglish (US)
Pages (from-to)1331-1339
Number of pages9
JournalStructure
Volume13
Issue number9
DOIs
StatePublished - Sep 2005

Bibliographical note

Funding Information:
We thank Marlijn Hoogendoorn for her expert help in producing and purifying the recombinant CD38 and Richard Gillilan for his help in crystallization. This work was supported by grants from the National Institutes of Health (NIH) to H.C.L. (GM60333 and GM61568) and to MacCHESS (RR01646). The crystallographic data were collected at the Cornell High Energy Synchrotron Source (CHESS), which is supported by the National Science Foundation and the NIH National Institute of General Medical Sciences under award DMR-0225180.

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