Lessons from bacterial homolog of tubulin, FtsZ for microtubule dynamics

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   Figure 1

   Tubulin and FtsZ show structural similarity. (A) Tubulin dimer with alpha and beta tubulin is shown as cartoon model. GTP and GDP nucleotides are bound to alpha and beta tubulin, respectively. They are shown as rainbow colored ball and stick models. (B) FtsZ is shown as a monomer with GDP bound to the N-terminal. N-terminals (blue) and C-terminals (pink) are separated by H7 helices (yellow). N-terminal regions show the typical nucleotide-binding motif with parallel beta sheets connected by alpha helices known as the Rossmann fold. From these structures, the differences in C-terminal region between the two proteins are evident. The figures were rendered using PyMOL. PDB ID for tubulin: 1SAO. PDB ID for FtsZ: 1FSZ.
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   Figure 2

   A model for microtubule assembly and disassembly is shown. (A) Free tubulin dimer bound to either GTP or GDP. (B) Tubulin dimers polymerize to form sheets of 13 protofilaments. (C) The sheets close to form a cylindrical tube. (D) Hydrolysis of GTP at the ends results in loss of GTP cap, exposing the GDP-tubulin lattice. GDP-tubulin units interact less strongly with each other, curling away from the tube and finally disassemble.
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   Figure 3

   A model for Z-ring assembly and disassembly. (A) Free FtsZ (monomer) exists predominantly as GTP-bound state. (B) GTP-FtsZ associates to form longitudinal filaments. (C) Protofilaments laterally contact to form a discontinuous Z-ring at the mid-cell region. (D) GTP hydrolysis leads to change in conformation as GDP-FtsZ is in curved state, which helps in membrane constriction. Finally Z-ring disassembles completely and cytokinesis occurs.
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   Figure 4

   Effects of CA-4 and compound 12 on microtubules. Compound 12 (panel A) depolymerizes microtubules (green) more strongly than CA-4 (panel B). Reproduced with permission from Chaudhary V, Venghateri JB, Dhaked HPS, Bhoyar AS, Guchhait SK & Panda D 2016 Novel combretastatin-2-aminoimidazole analogues as potent tubulin assembly inhibitors: exploration of unique pharmacophoric impact of bridging skeleton and aryl moiety. Journal of Medicinal Chemistry 59 3439–3451. Copyright 2016 American Chemical Society.
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   Figure 5

   SB-RA-2001 perturbed the Z-ring formation without affecting nucleoid segregation. The immunostaining of Bacillus subtilis 168 cells showing the localization of FtsZ (red) and DNA (blue) in the absence and presence of compound. This compound adversely affects the localization of FtsZ at mid-site of cell. Reproduced with permission from Singh D, Bhattacharya A, Rai A, Dhaked HPS, Awasthi D, Ojima I & Panda D 2014 SB-RA-2001 inhibits bacterial proliferation by targeting FtsZ assembly. Biochemistry 53 2979–2992; Copyright 2014 American Chemical Society. Figures available under the terms of the ACS AuthorChoice License.
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   Figure 6

   Effects of BT-benzo-29 on the localization of FtsZ and its associated proteins. (Panel A) The cell division proteins GFP-FtsZ, GFP-FtsA, GFP-ZapA and GFP-SepF localize at the center in the control cells. These proteins do not localize at mid-cell and diffuse throughout the length in the treated cells. Panel B shows the disrupting effect of BT-benzo-29 on the Z-ring without perturbation of the nuclear material. Reproduced with permission from Ray S, Jindal B, Kunal K, Surolia A & Panda D 2015 BT-benzo-29 inhibits bacterial cell proliferation by perturbing FtsZ assembly. FEBS Journal 282 4015–4033. Copyright 2015 FEBS.

• © 2017 Society for Endocrinology