ArticleThe Journal of biological chemistry2010
Stathmin and interfacial microtubule inhibitors recognize a naturally curved conformation of tubulin dimers.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 103 citations in OpenAlex.
- Frentizole, a Nontoxic Immunosuppressive Drug, and Its Analogs Display Antitumor Activity via Tubulin Inhibition.International journal of molecular sciences · 2023Article
- Protein Modelling and Molecular Docking Analysis of Fasciola hepatica β-Tubulin's Interaction Sites, with Triclabendazole, Triclabendazole Sulphoxide and Triclabendazole Sulphone.Acta parasitologica · 2023Article
- Repurposing drugs to treat trichinellosis: in vitro analysis of the anthelmintic activity of nifedipine and Chrysanthemum coronarium extract.BMC complementary medicine and therapies · 2023Article
- Identification of pyrrolo[3',4':3,4]cyclohepta[1,2-d][1,2]oxazoles as promising new candidates for the treatment of lymphomas.European journal of medicinal chemistry · 2023Article
- Molecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective.Drug discovery today · 2022Review
- Emerging role of microtubule-associated proteins on cancer metastasis.Frontiers in pharmacology · 2022Review
- Article
- GTP-dependent formation of straight tubulin oligomers leads to microtubule nucleation.The Journal of cell biology · 2021Article
- Pyrrolo[2',3':3,4]cyclohepta[1,2-Journal of medicinal chemistry · 2020Article
- The dynamic and structural properties of axonemal tubulins support the high length stability of cilia.Nature communications · 2019Article
- Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects.Frontiers in aging neuroscience · 2019Article
- Microtubule dynamics: moving toward a multi-scale approach.Current opinion in cell biology · 2018Review
- Heterogeneous Tau-Tubulin Complexes Accelerate Microtubule Polymerization.Biophysical journal · 2017Article
- GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe.Molecular biology of the cell · 2016Article
- Tau Binds to Multiple Tubulin Dimers with Helical Structure.Journal of the American Chemical Society · 2015Article
- Detailed Per-residue Energetic Analysis Explains the Driving Force for Microtubule Disassembly.PLoS computational biology · 2015Article
- Article
- The contribution of αβ-tubulin curvature to microtubule dynamics.The Journal of cell biology · 2014Review
- Synthesis of the new ring system bispyrido[4',3':4,5]pyrrolo [1,2-a:1',2'-d]pyrazine and its deaza analogue.Molecules (Basel, Switzerland) · 2014Article
- New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer.Journal of medicinal chemistry · 2014Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathmin-like domain of the RB3 protein (T(2)RB3). GTP hydrolysis following microtubule assembly induces protofilament curvature and disassembly. The conformation of the labile tubulin heterodimers is unknown. One important question is whether free GDP-tubulin dimers are straightened by GTP binding or if GTP-tubulin is also curved and switches into a straight conformation upon assembly. We have obtained insight into the bending flexibility of tubulin by analyzing the interplay of tubulin-stathmin association with the binding of several small molecule inhibitors to the colchicine domain at the tubulin intradimer interface, combining structural and biochemical approaches. The crystal structures of T(2)RB3 complexes with the chiral R and S isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl-carbamate, show that their binding site overlaps with colchicine ring A and that both complexes have the same curvature as unliganded T(2)RB3. The binding of these ligands is incompatible with a straight tubulin structure in microtubules. Analytical ultracentrifugation and binding measurements show that tubulin-stathmin associations (T(2)RB3, T(2)Stath) and binding of ligands (R, S, TN-16, or the colchicine analogue MTC) are thermodynamically independent from one another, irrespective of tubulin being bound to GTP or GDP. The fact that the interfacial ligands bind equally well to tubulin dimers or stathmin complexes supports a bent conformation of the free tubulin dimers. It is tempting to speculate that stathmin evolved to recognize curved structures in unassembled and disassembling tubulin, thus regulating microtubule assembly.
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