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The structure of a PKD domain from polycystin‐1: implications for polycystic kidney disease
Author(s) -
Bycroft Mark,
Bateman Alex,
Clarke Jane,
Hamill Stefan J.,
Sandford Richard,
Thomas Ruth L.,
Chothia Cyrus
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.2.297
Subject(s) - biology , polycystic kidney disease , polycystic kidney , pkd1 , domain (mathematical analysis) , disease , bioinformatics , kidney disease , computational biology , medicine , kidney , endocrinology , mathematical analysis , mathematics
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.