Abstract
The common liver fluke Fasciola hepatica causes an increasing burden on human and animal health, partly because of the spread of drug-resistant isolates. As a consequence, there is considerable interest in developing new drugs to combat liver fluke infections. A group of potential targets is a family of calcium-binding proteins which combine an N-terminal domain with two EF-hand motifs and a C-terminal domain with predicted similarity to dynein light chains (DLC-like domain). The function of these proteins is unknown, although in several species, they have been localised to the tegument, an important structure at the host-parasite interface. Here, we report the X-ray crystal structure of the DLC-like domain of F. hepatica calcium-binding protein 2 (FhCaBP2), solved using single-wavelength anomalous diffraction and refined at 2.3 Å resolution in two different crystal forms. The FhCaBP2 DLC-like domain has a structure similar to other DLC domains, with an anti-parallel β-sheet packed against an α-helical hairpin. Like other DLC domains, it dimerises through its β2-strand, which extends in an arch and forms the fifth strand in an extended β-sheet of the other monomer. The structure provides molecular details of the dimerisation of FhCaBP2, the first example from this family of parasite proteins.
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Acknowledgments
Crystallographic data was collected at beamline XALOC-BL13 at ALBA Synchrotron Light Facility with the collaboration of Fernando Gil and Jordi Juanhuix. MJvR thanks the Spanish Ministry of Economy and Competitiveness for grants BFU2011-24843 and BFU2014-53425-P. THN received a PhD fellowship from the Consejo Superior de Investigaciones Científicas and Vietnam Academy of Science and Technology. CMT is in receipt of a PhD studentship from the Department of Employment and Learning, Northern Ireland (DELNI, UK).
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Nguyen, T.H., Thomas, C.M., Timson, D.J. et al. Fasciola hepatica calcium-binding protein FhCaBP2: structure of the dynein light chain-like domain. Parasitol Res 115, 2879–2886 (2016). https://doi.org/10.1007/s00436-016-5046-x
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DOI: https://doi.org/10.1007/s00436-016-5046-x