Abstract

CD38 is a human lymphocyte differentiation antigen and multifunctional surface receptor with both enzymatic and cell adhesion functions. Ligation of CD38 with agonistic antibodies induces diverse effects in hematopoietic cells. As an enzyme CD38 synthesizes cADPR from NAD and hydrolyzes cADPR to ADPR. The existence of a transmembrane cell surface glycoprotein, which is both a receptor and an enzyme, presents an intriguing and as yet unanswered question: What is the function of this ectozyme? In B-cells CD38 functions as a co-receptor for BCR signaling. CD38 may also mediate ADP ribosylation of cell surface proteins as well as regulating insulin secretion and interacting with CD31 and the CD3/TCR complex. A structural investigation of CD38 is essential to understand the immunological significance of this multifunctional molecule. We seek time on BL 9-1/7-1 in order to collect high-resolution native data and heavy atom derivative data sets for initial structure determination and to subsequently elucidate the catalytic mechanism. A previous test done on BL 7-1 with a tiny crystal resulted in diffraction to almost 2.8 E. Beam time on BL 9-1/7-1 is requested in order to attain a high resolution structure to comprehend the reaction mechanism of CD38.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-20
Application #
6119535
Study Section
Project Start
1999-03-01
Project End
2000-04-14
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
20
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

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Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
Guillaume, Joren; Wang, Jing; Janssens, Jonas et al. (2017) Galactosylsphingamides: new ?-GalCer analogues to probe the F'-pocket of CD1d. Sci Rep 7:4276
Ishigami, Izumi; Zatsepin, Nadia A; Hikita, Masahide et al. (2017) Crystal structure of CO-bound cytochrome c oxidase determined by serial femtosecond X-ray crystallography at room temperature. Proc Natl Acad Sci U S A 114:8011-8016

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