The mechanical properties of kinesin-1: a holistic approach

Abstract

During the last 25 years, a vast amount of research has gone into understanding the mechanochemical cycle of kinesin-1 and similar processive motor proteins. An experimental method that has been widely used to this effect is the in vitro study of kinesin-1 molecules moving along microtubules while pulling a bead, the position of which is monitored optically while trapped in a laser focus. Analysing results from such experiments, in which thermally excited water molecules are violently buffeting the system components, can be quite difficult. At low loads, the effect of the mechanical properties of the entire molecule must be taken into account, as stalk compliance means the bead position recorded is only weakly coupled to the movement of the motor domains, the sites of ATP hydrolysis and microtubule binding. In the present review, findings on the mechanical and functional properties of the various domains of full-length kinesin-1 molecules are summarized and a computer model is presented that uses this information to simulate the motion of a bead carried by a kinesin molecule along a microtubule, with and without a weak optical trap present. A video sequence made from individual steps of the simulation gives a three-dimensional visual insight into these types of experiment at the molecular level.

Temporal and tissue specific gene expression patterns of the zebrafish kinesin-1 heavy chain family, kif5s, during development

“…H2 is especially important as it allows formation of the inactive folded conformation when cargo is not bound(Friedman and Vale, 1999; Hackney et al, 1992). The C-terminal tail region is known to mediate interaction with Kinesin Light Chains (KLCs) and various cargo(Jeppesen and Hoerber, 2012). …”

Conventional kinesin: Biochemical heterogeneity and functional implications in health and disease

“…Immunoelectron microscopy-based visualization of the purified conventional kinesin holoenzyme revealed kinesin-1 subunits as two 80 nm long rods, each featuring a globular head and a fan-shaped tail [4,40]. A molecular basis underlying this structure was illuminated after KIF5 protein sequences became available [52], and it is now clear that the overall protein domain organization of all KIF5 members within the kinesin-1 subfamily is highly conserved [reviewed in [45]]. A head motor region, located at the amino-terminus, comprises microtubule binding and ATPase hydrolysis domains responsible for the mechanochemical properties of conventional klnesis.…”

Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases

“…2). However, all kinesin-1s feature a highly conserved domain organization [reviewed in (Jeppesen and Hoerber, 2012)]. A head motor region, located at the amino-terminus, comprises the microtubule binding and ATPase hydrolysis domains responsible for the mechanochemical properties of the conventional klnesin holoenzyme.…”

“…The head and neck-linker domains are followed by a long stalk region containing a hinge and two coiled-coil domains with the first one responsible for dimerization of kinesin-1 subunits and the second involved in mediating interactions with KLC subunits. Finally, the extreme C-terminal tail of kinesin-1 comprises a small globular domain featuring the most divergent sequence stretches among kinesin-1 subfamily members (Jeppesen and Hoerber, 2012). …”