The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease

EMBO J. 1999 Jan 15;18(2):297-305. doi: 10.1093/emboj/18.2.297.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Conserved Sequence
  • DNA Primers / genetics
  • Escherichia coli / genetics
  • Fishes, Poisonous / genetics
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Polycystic Kidney, Autosomal Dominant / genetics*
  • Protein Conformation
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Proteins / genetics*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • TRPP Cation Channels

Substances

  • DNA Primers
  • Proteins
  • Recombinant Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein

Associated data

  • PDB/UNKNOWN