A bipolar kinesin

Abstract

Chromosome segregation during mitosis depends on the action of the mitotic spindle, a self-organizing, bipolar protein machine which uses microtubules (MTs) and their associated motors. Members of the BimC subfamily of kinesin-related MT-motor proteins are believed to be essential for the formation and functioning of a normal bipolar spindle. Here we report that KRP130, a homotetrameric BimC-related kinesin purified from Drosophila melanogaster embryos, has an unusual ultrastructure. It consists of four kinesin-related polypeptides assembled into a bipolar aggregate with motor domains at opposite ends, analogous to a miniature myosin filament. Such a bipolar 'minifilament' could crosslink spindle MTs and slide them relative to one another. We do not know of any other MT motors that have a bipolar structure.

Mutations in the human kinesin Eg5 that confer resistance to monastrol and S-trityl-l-cysteine in tumor derived cell lines

“…Eg5 from different species have been shown to function as tetramers [2,39,40] and thus under our experimental conditions Eg5 should be a promiscuous homotetramer composed of endogenous drug sensitive Eg5 and ectopically expressed drug resistant Eg5. If this is the case, then the observed resistance to either monastrol or STLC raises questions concerning the mode of displacement/processivity of Eg5 along microtubules.…”

“…Eg5 is a homotetrameric motor formed by the antiparallel arrangement of two dimers [2]. The Eg5 tetramer has the ability to crosslink antiparallel microtubules emanating from the two centrosomes at G2/M.…”

Prime movers: the mechanochemistry of mitotic kinesins

“…1a) absolutely requires KIF11 52 , which is the only member of the kinesin-5 family in humans 53 . KIF11 is built from two homodimers arranged in an antiparallel manner so that identical pairs of heads project from each end of the tetramer, forming a microtubule cross-linker 52,54,55 . The C-terminal tip of the KIF11 tail also contributes to microtubule binding 56 .…”

“…The proximal part of the N-terminal neck is positively charged and this accelerates the initial recruitment of the motor to the microtubule 54,176 . The next part of the N-terminal neck folds around and makes a helix that anneals to this KVD finger 175 .…”

Kinesin-5–dependent Poleward Flux and Spindle Length Control inDrosophilaEmbryo Mitosis

“…These motility events are driven by molecular-scale forces generated by mitotic kinesins and dyneins, together with dynamic microtubules (MTs), whose activities are controlled by a network of regulatory proteins, e.g., mitotic kinases, phosphatases, and proteolytic enzymes (Sharp et al, 2000c; BettencourtDias et al, 2004;Maiato and Sunkel, 2004;Rogers et al, 2005;Goshima et al, 2007). Among these mitotic proteins, the kinesin-5 motor is thought to play a key role (Cottingham et al, 1999;Valentine et al, 2006a;Civelekoglu-Scholey and Scholey, 2007).Purified kinesin-5 is a slow, modestly processive, plusend-directed bipolar homotetramer capable of cross-linking adjacent MTs and sliding apart antiparallel MTs in motility assays (Sawin et al, 1992;Cole et al, 1994;Kashina et al, 1996a;Kapitein et al, 2005;Tao et al, 2006;Valentine et al, 2006b;Krzysiak et al, 2008;Van den Wildenberg et al, 2008). In yeast cells the homotetrameric structure of kinesin-5 appears to be essential for mitosis (Hildebrandt et al, 2006), and in Drosophila embryos KLP61F displays dynamic properties consistent with an association with spindle MTs (Cheerambathur et al, 2008) and forms presumptive MT-MT cross-bridges (Sharp et al, 1999a).…”