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A high‐resolution structure of the EF‐hand domain of human polycystin‐2
Author(s) -
Allen Mark D.,
Qamar Seema,
Vadivelu Murali K.,
Sandford Richard N.,
Bycroft Mark
Publication year - 2014
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2513
Subject(s) - pkd1 , autosomal dominant polycystic kidney disease , ef hand , coiled coil , calcium binding protein , mutant , chemistry , population , membrane protein , cytoplasm , biophysics , crystallography , nuclear magnetic resonance spectroscopy , calcium , gene , biology , peptide sequence , membrane , biochemistry , genetics , stereochemistry , medicine , kidney , environmental health , organic chemistry
Autosomal dominant polycystic kidney disease (ADPKD) affects over 1:1000 of the worldwide population and is caused by mutations in two genes, PKD1 and PKD2 . PKD2 encodes a 968‐amino acid membrane spanning protein, Polycystin‐2 (PC‐2), which is a member of the TRP ion channel family. The C‐terminal cytoplasmic tail contains an EF‐hand motif followed by a short coiled‐coil domain. We have determined the structure of the EF‐hand region of PC‐2 using NMR spectroscopy. The use of different boundaries, compared with those used in previous studies, have enabled us to determine a high resolution structure and show that the EF hand motif forms a standard calcium‐binding pocket. The affinity of this pocket for calcium has been measured and mutants that both decrease and increase its affinity for the metal ion have been created.