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: M Bycroft, A Bateman, J Clarke, S J Hamill, R Sandford, R L Thomas, C Chothia
• Journal: The EMBO journal (EMBO J) Vol. 18 Issue 2 Pg. 297-305 (Jan 15 1999) ISSN: 0261-4189 [Print] England
• PMID: 9889186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, genetics)
• Recombinant Proteins (chemistry, genetics)
• TRPP Cation Channels