| Institution: | 1. Joint Center for Structural Genomics, http://www.jcsg.org;2. Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California 94025;3. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, United Kingdom;4. Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, California 92121;5. Center for Research in Biological Systems, University of California, San Diego, La Jolla, California 92093;6. Program on Bioinformatics and Systems Biology, Sanford‐Burnham Medical Research Institute, La Jolla, California 92037;7. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037;8. Photon Science, SLAC National Accelerator Laboratory, Menlo Park, California 94025 |
| Abstract: | Sufu (Suppressor 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 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 gonorrhoeae, at 1.4 Å 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 (r.m.s.d. of 2.6 Å over 93% of the NGO1391 protein), despite an extremely low sequence identity of ～15%. Subsequent sequence analysis revealed that NGO1391 defines a new subset of smaller, Sufu‐like proteins that are present in ～200 bacterial species and has resulted in expansion of the SUFU (PF05076) family in Pfam. |
