Download MendeleyStructure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches.
Leung, A.K., Lucile White, E., Ross, L.J., Reynolds, R.C., DeVito, J.A., Borhani, D.W.(2004) J Mol Biol 342: 953-970
- PubMed: 15342249
- DOI: https://doi.org/10.1016/j.jmb.2004.07.061
- Primary Citation of Related Structures:
1RLU, 1RQ2, 1RQ7 - PubMed Abstract:
We report three crystal structures of the Mycobacterium tuberculosis cell division protein FtsZ, as the citrate, GDP, and GTPgammaS complexes, determined at 1.89, 2.60, and 2.08A resolution. MtbFtsZ crystallized as a tight, laterally oriented dimer distinct from the longitudinal polymer observed for alphabeta-tubulin. Mutational data on Escherichia coli FtsZ suggest that this dimer interface is important for proper protofilament and "Z-ring" assembly and function. An alpha-to-beta secondary structure conformational switch at the dimer interface is spatially analogous to, and has many of the hallmarks of, the Switch I conformational changes exhibited by G-proteins upon activation. The presence of a gamma-phosphate in the FtsZ active site modulates the conformation of the "tubulin" loop T3 (spatially analogous to the G-protein Switch II); T3 switching upon gamma-phosphate ligation is directly coupled to the alpha-to-beta switch by steric overlap. The dual conformational switches observed here for the first time in an FtsZ link GTP binding and hydrolysis to FtsZ (and tubulin) lateral assembly and Z-ring contraction, and they are suggestive of an underappreciated functional analogy between FtsZ, tubulin and G-proteins.
Organizational Affiliation:
Drug Discovery Division, Southern Research Institute, Birmingham, AL 35205, USA.
