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

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

M Bycroft 1, A Bateman 1, J Clarke 1, S J Hamill 1, R Sandford 1, R L Thomas 1, C Chothia 1
PMCID: PMC1171124  PMID: 9889186

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.

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Selected References

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