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A high-resolution structure of the EF-hand domain of human polycystin-2

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  • Mark D. Allen
  • Seema Qamar
  • Murali K. Vadivelu
  • Richard N. Sandford
  • Mark Bycroft
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.
Original languageEnglish
Pages (from-to)1301-1308
JournalProtein Science
Volume23
Issue number9
Early online date22 Jul 2014
DOIs
Publication statusPublished - 1 Sep 2014
Externally publishedYes

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