[HTML][HTML] The structure of a PKD domain from polycystin‐1: implications for polycystic kidney disease

M Bycroft, A Bateman, J Clarke, SJ Hamill… - The EMBO …, 1999 - embopress.org
M Bycroft, A Bateman, J Clarke, SJ Hamill, R Sandford, RL Thomas, C Chothia
The EMBO journal, 1999embopress.org
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 β‐sandwich fold. Although this fold is common to a number …
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 β‐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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