These motors were made for walking

Abstract

Kinesins are a diverse group of ATP-dependent motor proteins that transport cargos along microtubules (MTs) and change the organization of MT networks. Shared among all kinesins is a ~ 40 kDa motor domain that has evolved an impressive assortment of motility and MT remodeling mechanisms as a result of subtle tweaks and edits within its sequence.Several elegant studies of different kinesin isoforms have exposed the purpose of structural changes in the motor domain as it engages and leaves the MT. However, few studies have compared the sequences and MT contacts of these kinesins systematically. Along with clever strategies to trap kinesin-tubulin complexes for X-ray crystallography, new advancements in cryo-electron microscopy have produced a burst of high-resolution structures that show kinesin-MT interfaces more precisely than ever. This review considers the MT interactions of kinesin subfamilies that exhibit significant differences in speed, processivity, and MT remodeling activity. We show how their sequence variations relate to their tubulin footprint and, in turn, how this explains the molecular activities of previously characterized mutants. As more high-resolution structures become available, this type of assessment will quicken the pace toward establishing each kinesin's designfunction relationship.

Hybrid method for representing ions in implicit solvation calculations

“…This is consistent with the distribution of charges on the interface of the kinesin motor domain and the tubulin dimer, as shown in Fig. 11 B and D. Most kinesins interact with only β-tubulin [53] , [54] , but kinesin-5 (cut7) interacts with both α- and β-tubulin. This may imply the bidirectional characteristic of kinesin-5 (cut-7) [41] .…”

Biological nanomotors, driving forces of life

“…Our current understanding of the transitions in the motor cycle are too limited to fully account for and predict what tunes force production. In addition, too little is known about how the track triggers these transitions, how divergence in the track binding regions can tune motor properties [14,49] and how motors resist detachment from the track when opposite force is imposed on them. Ultimately, motility properties are governed by the rate of the transitions between states of the motor cycle, in particular those that occur while the motor is bound to the track.…”

“…Notre compréhension actuelle des transitions dans le cycle moteur est trop limitée pour expliquer et prédire comment la production de force est réglée. En outre, on en sait trop peu sur la façon avec laquelle la piste déclenche ces transitions, et comment le site d'interaction à la piste, variable d'un moteur à l'autre, pourrait contribuer à l'ajustement des propriétés du moteur [14,49]. Enfin, les facteurs importants pour qu'un moteur résiste au détachement de la piste lorsqu'une force opposée est imposée sont aujourd'hui inconnus.…”

Negative Modulation of the Angiogenic Cascade Induced by Allosteric Kinesin Eg5 Inhibitors in a Gastric Adenocarcinoma In Vitro Model

“…All kinesins present a motor domain named “head”, with high grade retained within families, a globular tail, and a junction region between head and tail, named the stalk. The head motor domain has a specific structure designed to allow a cyclic attachment-detachment from microtubules, due to the energy obtained from ATP hydrolysis [ 10 ], and it is located differently in each subfamily. It is present in the N -terminal or C -terminal region or in the middle of the protein, in N-kinesins, C-kinesins, and M-kinesins, respectively.…”