GNF ID 100504: The crystal structure of Neisseria gonorrhoea NGO1391 defines a novel set of bacterial proteins that are similar to the N-terminal domain of human Sufu (Suppresor of Fused)

Sufu (Suppresor of Fused), a two domain protein, plays a critical role in regulating Hedgehog signaling and is conserved from flies to humans. A few bacterial Sufu-like proteins have previously been identified based on sequence similarity to the N-terminal domain of eukaryotic Sufu proteins, but none of them have been structurally or biochemically characterized and their function in bacteria is unknown. We have determined the crystal structure of a more distantly related Sufu-like homolog, NGO1391 from Neisseria gonorrhea, at 1.4 A resolution, which provides the first biophysical characterization of a bacterial Sufu-like protein. The structure revealed a striking similarity to the N-terminal domain of human Sufu, despite an extremely weak sequence identity of ~15%. Subsequent sequence analysis revealed that NGO1391 defines a new set of smaller Sufu-like proteins from ~200 bacterial species and has resulted in an expansion of the Sufu family in Pfam.