Motor proteins of the kinesin family. Structures, variations, and nucleotide binding sites.

Microtubule-dependent motors of the kinesin family convert the energy from ATP hydrolysis into mechanical work in order to transport vesicles and organelles along microtubules. The motor domains of several kinesins have been solved by X-ray diffraction, but the conformational changes associated with force development remain unknown. Here we describe conformational properties of kinesin that might be related to the mechanism of action. First, we have evaluated the conformational variability among all known kinesin structures and find they are concentrated in six areas, most of which are functionally important either in microtubule binding or in linking the core motor to the stalk. Secondly, we show that there is an important difference between kinesins when compared with myosins or GTPases (with which kinesin motor domains bear structural and catalytic similarities); in the diphosphate-state (with bound ADP), all kinesins show a 'tight' nucleotide-binding pocket, comparable with myosin or GTPases in the triphosphate state, whose nucleotide-binding pockets become open, or 'loose', following nucleotide hydrolysis. Thus, kinesin-ADP appears to be in a tense state, resembling that observed in myosin-ATP or p21ras-GTP.

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