Abstract
The human serum vitamin D-binding protein (DBP) has many physiologically important functions, ranging from transporting vitamin D3 metabolites, binding and sequestering globular actin and binding fatty acids to functioning in the immune system. Here we report the 2.3 Å crystal structure of DBP in complex with 25-hydroxyvitamin D3, a vitamin D3 metabolite, which reveals the vitamin D-binding site in the N-terminal part of domain I. To more explicitly explore this, we also studied the structure of DBP in complex with a vitamin D3 analog. Comparisons with the structure of human serum albumin, another family member, reveal a similar topology but also significant differences in overall, as well as local, folding. These observed structural differences explain the unique vitamin D3-binding property of DBP.
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Acknowledgements
We thank A. Norman and W. Okamura for their generous gift of the JY analog; H. De Bondt for critical discussions; A. Gonzalez for help with the MAD data collection and processing; L. Barron for careful reading of the manuscript; the staff of the DESY synchrotron EMBL beam lines and of the ELETTRA 5.1R beam line for their technical support during data collection; the European Community for their traveling support to the EMBL Hamburg Outstation and to ELETTRA through their Access to Research Infrastructure action. This work was in part supported by the K.U.Leuven Research Fund and by the Fund for Scientific Research Flanders, Belgium.
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Verboven, C., Rabijns, A., De Maeyer, M. et al. A structural basis for the unique binding features of the human vitamin D-binding protein. Nat Struct Mol Biol 9, 131–136 (2002). https://doi.org/10.1038/nsb754
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DOI: https://doi.org/10.1038/nsb754
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