Kinesin's backsteps under mechanical load.
Kinesins move processively toward the plus end of microtubules by hydrolyzing ATP for each step. From an enzymatic perspective, the mechanism of mechanical motion coupled to the nucleotide chemistry is often well explained using a single-loop cyclic reaction. However, several difficulties arise in interpreting kinesin's backstepping within this framework, especially when external forces oppose the motion of kinesin. We review evidence, such as an ATP-independent stall force and a slower cycle time for backsteps, that has emerged to challenge the idea that kinesin backstepping is due to ATP synthesis, i.e., the reverse cycle of kinesin's forward-stepping chemomechanics. Supplementing the conventional single-loop chemomechanics with routes for ATP-hydrolyzing backward steps and nucleotide-free steps, especially under load, gives a better physical interpretation of the experimental data on backsteps.
Hyeon
Changbong
C
Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea.
Klumpp
Stefan
S
Onuchic
José N
JN
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001696:Biomechanical Phenomena; D006868:Hydrolysis; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D009068:Movement; D011487:Protein Conformation; D013816:Thermodynamics; D016474:Weight-Bearing
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D016547:Kinesins