A conformationally heterogeneous bending pivot enables bent-to-straight transition in the central helix of mycobacterial FtsZ
Conformational changes in the central helix at the inter-domain cleft of bacterial treadmilling motor protein FtsZ are coupled to polymerization. Central helix of mycobacterial FtsZ interconverts between a bent and a straight form, with an unknown mechanism. We probed the mechanism of this conformational switching in the central helix of mycobacterial FtsZ using multi-temperature synchrotron crystallography at 20 {o}C, 30 {o}C, 37 {o}C and -173 {o}C temperatures. A comparison of the resultant crystal structures of FtsZ revealed altered conformations at the bending pivot of the bent central helix inside the inter-domain cleft. Further, ensemble modeling of FtsZ structure shows that this bending pivot is labile at near-physiological temperatures. Conformational fluctuations in this pivot region resulted in breakage of regular alpha helical hydrogen bonds that likely made the central helix easily bendable. These fluctuations are largely arrested in the straightened form of the central helix in comparison to the bent form. To summarize, multi-temperature crystallography combined with ensemble modeling suggest that conformational heterogeneity and associated perturbations of helix-forming interactions in the bending pivot can trigger bent-to-straight conformational transition in the central helix of mycobacterial FtsZ. This work demonstrates the effectiveness of multi-temperature crystallography in delineating the mechanisms of conformational changes in protein machines.