Structure and thermodynamics of the tubulin–stathmin interaction

Steinmetz, Michel O.

doi:10.1016/j.jsb.2006.07.018

Cited by 76 publications

(105 citation statements)

References 51 publications

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“…According to our AUC and previously published data [6,24], VLB and stathmin binding to tubulin are coupled to either tubulin assembly or disassembly ( Figs. 1 and 2).…”

Section: Thermodynamic Parameters Of Tubulin Complex Formationsupporting

confidence: 66%

Stathmin/Op18 is a novel mediator of vinblastine activity

et al. 2008

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Microtubule (MT) dynamic instability is tightly regulated by stabilizing and destabilizing proteins, the latter being exemplified by stathmin/Op18, a protein known to destabilize MTs. Studies in cells have indicated that the level of stathmin expression modifies the cytotoxicity of antimicrotubule drugs, such as vinblastine (VLB). Using isothermal titration calorimetry and analytical ultracentrifugation, we show that VLB increases the affinity of stathmin for tubulin 50-fold (and vice versa). These results are the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and reveal a new mechanism of action for VLB. Structured summary:MINT-6603918: tubulin beta (uniprotkb:Q9H4B7), tubulin alpha (uniprotkb:Q71U36) and stathmin (uniprotkb:Q71U36) physically interact (MI:0218) by cosedimentation (MI:0027) MINT-6603930: tubulin alpha (uniprotkb:Q71U36) physically interacts (MI:0218) with tubulin beta (uniprotkb:Q9H4B7) and stathmin (uniprotkb:P16949) by isothermal titration calorimetry (MI:0065)

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“…According to our AUC and previously published data [6,24], VLB and stathmin binding to tubulin are coupled to either tubulin assembly or disassembly ( Figs. 1 and 2).…”

Section: Thermodynamic Parameters Of Tubulin Complex Formationsupporting

confidence: 66%

Stathmin/Op18 is a novel mediator of vinblastine activity

et al. 2008

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“…Stathmin inhibits microtubule assembly by sequestering tubulin dimers and stimulates depolymerization at microtubule ends (14). It is tempting to speculate that proteins of the stathmin family co-evolved with tubulin to recognize the inactive curved conformations of unassembled and disassembling tubulin and in this manner regulate microtubules.…”

Section: Discussionmentioning

confidence: 99%

“…Stathmin (11) is a cellular microtubule inhibitor (12), which forms a tight complex with two ␣␤-tubulin dimers (13), T 2 Stath, 5 binding along their sides and capping the ␣-end (14). T 2 Stath has been shown to be curved by electron microscopy, and it does not polymerize into microtubules (15).…”

mentioning

confidence: 99%

“…Proteins of the stathmin family are pivotal microtubule regulators implicated in signal transduction and disease (for reviews, see Refs. 11,14). Only two atomic structures of ␣␤-tubulin are currently known: One is GDP-tubulin in straight antiparallel protofilaments of two-dimensional zinc sheets stabilized by taxol (16,17), that has been employed to construct pseudo-atomic models of microtubules, which have parallel protofilaments, from their electron microscopy maps (18).…”

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confidence: 99%

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Stathmin and Interfacial Microtubule Inhibitors Recognize a Naturally Curved Conformation of Tubulin Dimers

Barbier

Dorléans

Devred

et al. 2010

Journal of Biological Chemistry

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Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathminlike 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 tubulinstathmin 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.Microtubules are essential for eukaryotic chromosome segregation, cellular architecture and intracellular trafficking, among other processes. Understanding microtubule dynamics, regulation, and organization requires knowledge of the nucleotide-regulated assembly switch of tubulin. Microtubules are hollow cylinders made of protofilaments of ␣␤-tubulin dimers in head to tail association, forming a pseudohelical lattice (1). The functional assembly-disassembly cycle of a ␣␤-tubulin molecule includes activation by GTP binding at the ␤-subunit, polymerization into microtubules, GTP hydrolysis at the ␤-␣ interdimer interface and depolymerization of GDP-tubulin, followed by replacement by GTP. Vectorial polymerization and GTP hydrolysis combine with tubulin structural plasticity in microtubule dynamics (2). Depolymerizing microtubule ends show characteristic curled protofilaments, whereas relatively straight sheets form at growing ends (3, 4). GDP-tubulin does not assemble into microtubules, but forms double rings (5), which also form upon microtubule depolymerization (6) and correspond to curved microtubule protofilaments (7,8). The tendency of GDP-tubulin to curve is thought to strain the microtubule lattice, causing disassembly when the terminal cap of GTP-bound tubulin...

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“…4 Thus, microtubules possess intrinsic dynamic properties, 5 tuned by a wide repertoire of cellular effectors, underlying their versatile architectures in cells. 2 Some microtubule modulators bind directly to microtubules (motors, microtubule-associated proteins), 6 while others bind to tubulin dimers (stathmin), 7 sever microtubules (spastin, katanin) 8 or chemically modify tubulin subunits (kinases, phosphatases, tubulin-modifying enzymes). 9 Members of the family of tubulin-modifying enzymes catalyze reversible posttranslational modifications including detyrosination, polyglutamylation, glycylation and acetylation.…”

Section: Introductionmentioning

confidence: 99%

CAP-Gly proteins contribute to microtubule-dependent trafficking via interactions with the C-terminal aromatic residue of α-tubulin

2017

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SUMMARYIn mammals, the C-terminal tyrosine residue of a-tubulin is subjected to removal/re-addition cycles resulting in tyrosinated microtubules and detyrosinated Glu-microtubules. CLIP170 and its yeast ortholog (Bik1) interact weakly with Glu-microtubules. Recently, we described a Microtubule-Rho1-and Bik1-dependent mechanism involved in Snc1 routing. Here, we further show a contribution of the yeast p150Glued ortholog (Nip100) in Snc1 trafficking. Both CLIP170 and p150Glued are CAPGly-containing proteins that belong to the microtubule Cend-tracking protein family (known as CTips). We discuss the CTips-dependent role of microtubules in trafficking, the role of CAP-Gly proteins as possible molecular links between microtubules and vesicles, as well as the contribution of the Rho1-GTPase to the regulation of the CTips repertoire and the partners associated with microtubules.

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Structure and thermodynamics of the tubulin–stathmin interaction

Cited by 76 publications

References 51 publications

Stathmin/Op18 is a novel mediator of vinblastine activity

Stathmin/Op18 is a novel mediator of vinblastine activity

Stathmin and Interfacial Microtubule Inhibitors Recognize a Naturally Curved Conformation of Tubulin Dimers

CAP-Gly proteins contribute to microtubule-dependent trafficking via interactions with the C-terminal aromatic residue of α-tubulin

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