A high-resolution structure of the EF-hand domain of human polycystin-2 |
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| Authors: | Mark D Allen Seema Qamar Murali K Vadivelu Richard N Sandford Mark Bycroft |
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| Affiliation: | 1MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, United Kingdom;2Department of Clinical Neurosciences, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, United Kingdom;3Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, United Kingdom |
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| Abstract: | 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. |
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| Keywords: | ADPKD polycystin-2 EF-hand solution structure NMR ITC mutagenesis |
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