A mechanism for microtubule depolymerization by KinI kinesins.
Whereas most kinesins motor along microtubules, KinI kinesins are microtubule depolymerizing machines. Surprisingly, we found that a KinI fragment consisting of only the motor core is capable of ATP-dependent depolymerization. The motor binds along microtubules in all nucleotide states, but in the presence of AMPPNP, microtubule depolymerization also occurs. Structural characterization of the products of AMPPNP-induced destabilization revealed a snapshot of the disassembly machine in action as it precisely deformed a tubulin dimer. While conventional kinesins use the energy of ATP binding to execute a "powerstroke," KinIs use it to bend the underlying protofilament. Thus, the relatively small class-specific differences within the KinI motor core modulate a fundamentally conserved mode of interaction with microtubules to produce a unique depolymerizing activity.
Moores
Carolyn A
CA
Department of Cell Biology, CB227, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Yu
Ming
M
Guo
Jun
J
Beraud
Christophe
C
Sakowicz
Roman
R
Milligan
Ronald A
RA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D001704:Biopolymers / Q000378:metabolism; D019281:Dimerization; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D001704:Biopolymers; D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D016547:Kinesins