Insight into the molecular mechanism of the multitasking kinesin-8 motor.
Members of the kinesin-8 motor class have the remarkable ability to both walk towards microtubule plus-ends and depolymerise these ends on arrival, thereby regulating microtubule length. To analyse how kinesin-8 multitasks, we studied the structure and function of the kinesin-8 motor domain. We determined the first crystal structure of a kinesin-8 and used cryo-electron microscopy to calculate the structure of the microtubule-bound motor. Microtubule-bound kinesin-8 reveals a new conformation compared with the crystal structure, including a bent conformation of the α4 relay helix and ordering of functionally important loops. The kinesin-8 motor domain does not depolymerise stabilised microtubules with ATP but does form tubulin rings in the presence of a non-hydrolysable ATP analogue. This shows that, by collaborating, kinesin-8 motor domain molecules can release tubulin from microtubules, and that they have a similar mechanical effect on microtubule ends as kinesin-13, which enables depolymerisation. Our data reveal aspects of the molecular mechanism of kinesin-8 motors that contribute to their unique dual motile and depolymerising functions, which are adapted to control microtubule length.
Peters
Carsten
C
Institute of Structural and Molecular Biology, Birkbeck College, London, UK.
Brejc
Katjuša
K
Belmont
Lisa
L
Bodey
Andrew J
AJ
Lee
Yan
Y
Yu
Ming
M
Guo
Jun
J
Sakowicz
Roman
R
Hartman
James
J
Moores
Carolyn A
CA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D000255:Adenosine Triphosphate; D016547:Kinesins
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