title: Fasciola hepatica calcium-binding protein FhCaBP2: structure of the dynein light chain-like domain.
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.
authors.affiliation: Dpto de Estructura de Macromoleculas, Centro Nacional de Biotecnologia-CSIC, calle Darwin 3, E-28049, Madrid, Spain.|Genetic Engineering Laboratory, Institute of Biotechnology (IBT-VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
authors.forename: Thanh H
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.|Institute for Global Food Security, Queen's University Belfast, 18-30 Malone Road, Belfast, BT9 5BN, UK.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Thomas
authors.affiliation: School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.|School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Timson
authors.affiliation: Dpto de Estructura de Macromoleculas, Centro Nacional de Biotecnologia-CSIC, calle Darwin 3, E-28049, Madrid, Spain. mjvanraaij@cnb.csic.es.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van Raaij
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004398:Dyneins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020832:EF Hand Motifs; D005210:Fasciola hepatica / Q000235:genetics / Q000378:metabolism*; D005211:Fascioliasis / Q000469:parasitology*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D000072417:Protein Domains; D011994:Recombinant Proteins
chemical_list: D002135:Calcium-Binding Proteins; D015801:Helminth Proteins; D011994:Recombinant Proteins; D004398:Dyneins
keywords: Calcium-binding protein; Crystal structure; Dynein light chain; Helminth protein; Liver fluke