03/01/2011
X-Ray Diffraction Data Provide First Insights into Key Tuberculosis (TB) Mechanism
Summary
TB infects a third of the world’s population. One key to the TB bacterium’s survival in human cells is its protein-recycling mechanism. Researchers seek to target this system by understanding the way in which proteins destined for degradation are recognized by the microbe’s proteasome before they enter that complex. A structural study at the National Synchrotron Light Source revealed the portion of the bacterial proteasome that identifies the unwanted protein’s “kiss of death” marker sequence, as well as structures of this sequence as it binds to the proteasome. These structures suggest a mechanism by which coiled, tentacle-like arms protruding from the proteasome identify the death-sentence label, causing a series of protein-folding maneuvers that pull the doomed protein into the degradation chamber. These details may provide highly specific targets for the development of new anti-TB therapies.
References
Wang, T., K. H. Darwin, and H. Li. 2010. “Binding-Induced Folding of Prokaryotic Ubiquitin-Like Protein on the Mycobacterium Proteasomal ATPase Targets Substrates for Degradation,” Nature Structural and Molecular Biology 17, 1352–57.