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Article Dans Une Revue Journal of Biological Chemistry Année : 2012

Kif2C minimal functional domain has unusual nucleotide binding properties that are adapted to microtubule depolymerization.

Weiyi Wang
  • Fonction : Auteur
Qiyang Jiang
  • Fonction : Auteur
David Cornu
Benoît Gigant
Marcel Knossow
  • Fonction : Auteur
Chunguang Wang
  • Fonction : Auteur

Résumé

The kinesin-13 Kif2C hydrolyzes ATP and uses the energy released to disassemble microtubules. The mechanism by which this is achieved remains elusive. Here we show that Kif2C-(sN+M), a monomeric construct consisting of the motor domain with the proximal part of the N-terminal Neck extension but devoid of its more distal, unstructured, and highly basic part, has a robust depolymerase activity. When detached from microtubules, the Kif2C-(sN+M) nucleotide-binding site is occupied by ATP at physiological concentrations of adenine nucleotides. As a consequence, Kif2C-(sN+M) starts its interaction with microtubules in that state, which differentiates kinesin-13s from motile kinesins. Moreover, in this ATP-bound conformational state, Kif2C-(sN+M) has a higher affinity for soluble tubulin compared with microtubules. We propose a mechanism in which, in the first step, the specificity of ATP-bound Kif2C for soluble tubulin causes it to stabilize a curved conformation of tubulin heterodimers at the ends of microtubules. Data from an ATPase-deficient Kif2C mutant suggest that, then, ATP hydrolysis precedes and is required for tubulin release to take place. Finally, comparison with Kif2C-Motor indicates that the binding specificity for curved tubulin and, accordingly, the microtubule depolymerase activity are conferred to the motor domain by its N-terminal Neck extension.

Domaines

Chimie organique

Dates et versions

hal-00741318 , version 1 (12-10-2012)

Identifiants

Citer

Weiyi Wang, Qiyang Jiang, Manuela Argentini, David Cornu, Benoît Gigant, et al.. Kif2C minimal functional domain has unusual nucleotide binding properties that are adapted to microtubule depolymerization.. Journal of Biological Chemistry, 2012, 287 (18), pp.15143-53. ⟨10.1074/jbc.M111.317859⟩. ⟨hal-00741318⟩
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