Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3.

The Bowie lab uncovered the structural basis for autosomal dominant polycystic kidney disease, the most common genetic disorder leading to end-stage renal failure in humans. The team, lead by Catherine Leettola discovered the identities of the pair of proteins which interact normally in healthy patients but fail to interact in patients affected by the disease (ANKS3 and ANKS6).

These binding partners share a fold known as the “sterile alpha motif” or SAM domain, which has been characterized as a protein-protein interaction domain in several other proteins of medical importance. The team solved the crystal structure of the ANKS3-ANKS6 interacting pair and revealed how a mutation associated with disease disrupts their interaction.