title: A structural model of a seven-transmembrane helix receptor: the Duffy antigen/receptor for chemokine (DARC).
abstract: The Duffy antigen/receptor for chemokine (DARC) is an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi) and for chemokines. In contrast to other chemokine receptors, DARC is a promiscuous receptor that binds chemokines of both CC and CXC classes. The four extracellular domains (ECDs) of DARC are essential for its interaction with chemokines, whilst the first (ECD1) is sufficient for the interaction with malaria erythrocyte-binding protein. In this study, we elaborate and analyze structural models of the DARC. The construction of the 3D models is based on a comparative modeling process and on the use of many procedures to predict transmembrane segments and to detect far homologous proteins with known structures. Threading, ab initio, secondary structure and Protein Blocks approaches are used to build a very large number of models. The conformational exploration of the ECDs is performed with simulated annealing. The second and fourth ECDs are strongly constrained. On the contrary, the ECD1 is highly flexible, but seems composed of three consecutive regions: a small beta-sheet, a linker region and a structured loop. The chosen structural models encompass most of the biochemical features and reflect the known experimental data. They may be used to analyze functional interaction properties.
authors.affiliation: Equipe de Bioinformatique Génomique et Moléculaire (EBGM), INSERM U 726, Université Denis DIDEROT-Paris 7, case 7113, 2, place Jussieu, 75251 Paris, France. debrevern@ebgm.jussieu.fr
authors.forename: A G
authors.initials: AG
authors.lastname: de Brevern
authors.forename: H
authors.initials: H
authors.lastname: Wong
authors.forename: C
authors.initials: C
authors.lastname: Tournamille
authors.forename: Y
authors.initials: Y
authors.lastname: Colin
authors.forename: C
authors.initials: C
authors.lastname: Le Van Kim
authors.forename: C
authors.initials: C
authors.lastname: Etchebest
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019742:Chemokines, CC / Q000097:blood* / Q000737:chemistry; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D004375:Duffy Blood-Group System / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry; D000882:Haplorhini; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016790:Plasmodium knowlesi; D010966:Plasmodium vivax; D011956:Receptors, Cell Surface / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D055672:Static Electricity; D040681:Structural Homology, Protein
chemical_list: C473745:ACKR1 protein, human; D019742:Chemokines, CC; D004375:Duffy Blood-Group System; D006023:Glycoproteins; D011956:Receptors, Cell Surface; C029236:glycoprotein EDC1, human