title: The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease.
abstract: Most cases of autosomal dominant polycystic kidney disease (ADPKD) are the result of mutations in the PKD1 gene. The PKD1 gene codes for a large cell-surface glycoprotein, polycystin-1, of unknown function, which, based on its predicted domain structure, may be involved in protein-protein and protein-carbohydrate interactions. Approximately 30% of polycystin-1 consists of 16 copies of a novel protein module called the PKD domain. Here we show that this domain has a beta-sandwich fold. Although this fold is common to a number of cell-surface modules, the PKD domain represents a distinct protein family. The tenth PKD domain of human and Fugu polycystin-1 show extensive conservation of surface residues suggesting that this region could be a ligand-binding site. This structure will allow the likely effects of missense mutations in a large part of the PKD1 gene to be determined.
authors.affiliation: MRC Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW. mb10031@cus.cam.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Bycroft
authors.forename: A
authors.initials: A
authors.lastname: Bateman
authors.forename: J
authors.initials: J
authors.lastname: Clarke
authors.forename: S J
authors.initials: SJ
authors.lastname: Hamill
authors.forename: R
authors.initials: R
authors.lastname: Sandford
authors.forename: R L
authors.initials: RL
authors.lastname: Thomas
authors.forename: C
authors.initials: C
authors.lastname: Chothia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005400:Fishes, Poisonous / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D050396:TRPP Cation Channels
chemical_list: D017931:DNA Primers; D011506:Proteins; D011994:Recombinant Proteins; D050396:TRPP Cation Channels