Technical Highlight - February 2011
Short description: Combining structural and computational methods helps to define a family of proteins.
In humans, the Suppressor of Fused (SUFU) protein regulates Hedgehog (HH) signaling by binding Gli when inactive, and Fused when active. Until recently, there were 20 eukaryotic and 13 prokaryotic members in the SUFU family (Pfam PF05076), although the function of the bacterial Sufu-like proteins is not clear, as bacteria lack the HH signaling pathway. Now, Wilson and colleagues from the Protein Structure Initiative Joint Center for Structural Genomics (PSI JCSG) have described the crystal structure of Neisseria gonorrhoeae NGO1391 and defined the key characteristics of bacterial Sufu-like proteins.
NGO1391 is likely to exist as a monomer in solution, and it consists of a bulky N-terminal region with a long C-terminal tail lacking secondary structure and a hydrophobic cleft formed near the C terminus, which bound a glycerol molecule from the cryoprotectant. The protein shares significant structural similarity with the N-terminal domain of human SUFU, despite low sequence identity of only ∼15%.
Turning to a computational approach, the authors utilized successive rounds of PSI-BLAST and identified approximately 300 additional bacterial Sufu-like proteins. These were added to the Pfam PF05076 family; the full family now contains 341 proteins representing 31 eukaryotic and 220 bacterial species. Interestingly, the majority of residues that are conserved across the entire family are in the protein core, not surface exposed. The residues forming the hydrophobic cleft in NGO1391 are also largely conserved. Future experiments will be needed to address the function of this suddenly very large family of bacterial proteins, and this structural and computational characterization of the family will be instrumental to those efforts.
D. Das et al. The crystal structure of a bacterial Sufu-like protein defines a novel group of bacterial proteins that are similar to the N-terminal domain of human Sufu.
Protein Sci. 19, 2131-2140 (2010). doi:10.1002/pro.497