23 research outputs found
Template-free 13-protofilament microtubuleâMAP assembly visualized at 8 A resolution
Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Ă
structure of doublecortin (DCX)-stabilized MTs. Because of DCXâs unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulinâtubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCXâs exquisite binding selectivity uncovers important insights into regulation of cellular MTs
Tubulin-binding dibenz[c,e]oxepines: Part 2 Structural variation and biological evaluation as tumour vasculature disrupting agents
5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin αÎČ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4
A New Observer Design for Aging Detection of Supercapacitors
International audienc
Microtubule-Destabilizing Agents: Structural and Mechanistic Insights from the Interaction of Colchicine and Vinblastine with Tubulin
International audienc
Induction machine control in presence of magnetic hysteresis. Modelling and speed reference tracking
International audienceThe problem of controlling induction machine speed has generally been dealt with using standard models i.e. those based on the assumption that the magnetic characteristic is linear. In coherence with this assumption, most control strategies involved rotor flux regulation around a fixed nominal value. As a matter of fact, optimal performance operation (e.g. maximal efficiency, maximal torque, unitary power factor...) are not achievable using constant flux reference especially when facing wide range load variations. But, control strategies involving wide range flux reference variations can not be obtained without accounting for the nonlinearity of the machine magnetic characteristic. In the present work, we propose a new speed control strategy based on a new machine model that accounts for the magnetic characteristic hysteresis and saturation. A speed controller is designed using a nonlinear design technique. The performances of the proposed control strategy are formally analysed and their supremacy with respect to the standard control solution is illustrated through a simulation study, using a 7.5 KW machine
Ribonucleases J1 andJ2 form a complex with altered enzyme behaviour
International audienc
Ribonucleases J1 andJ2 form a complex with altered enzyme behaviour
International audienc