[HTML][HTML] Domain mapping of the polycystin-2 C-terminal tail using de novo molecular modeling and biophysical analysis
In polycystic kidney disease (PKD), polycystin-2 (PC2) is frequently mutated or truncated in
the C-terminal cytoplasmic tail (PC2-C). The currently accepted model of PC2-C consists of
an EF-hand motif overlapping with a short coiled coil; however, this model fails to explain the
mechanisms by which PC2 truncations C-terminal to this region lead to PKD. Moreover,
direct PC2 binding to inositol 1, 4, 5-trisphosphate receptor, KIF3A, and TRPC1 requires
residues in PC2-C outside this region. To address these discrepancies and investigate the …
the C-terminal cytoplasmic tail (PC2-C). The currently accepted model of PC2-C consists of
an EF-hand motif overlapping with a short coiled coil; however, this model fails to explain the
mechanisms by which PC2 truncations C-terminal to this region lead to PKD. Moreover,
direct PC2 binding to inositol 1, 4, 5-trisphosphate receptor, KIF3A, and TRPC1 requires
residues in PC2-C outside this region. To address these discrepancies and investigate the …