Modeling motility of the kinesin dimer from molecular properties of individual monomers.
Conventional kinesin is a homodimeric motor protein that unidirectionally transports organelles along filamentous microtubule (MT) by hydrolyzing ATP molecules. There remain two central questions in biophysical studies of kinesin: (1) the molecular physical mechanism by which the kinesin dimer, made of two sequentially identical monomers, selects a unique direction (MT plus end) for long-range transport and (2) the detailed mechanisms by which local molecular properties of individual monomers affect the motility properties of the dimer motor as a whole. On the basis of a previously proposed molecular physical model for the unidirectionality of kinesin, this study investigates the synergic motor performance of the dimer from well-defined molecular properties of individual monomers. During cargo transportation and also in single-molecule mechanical measurements, a load is often applied to the coiled-coil dimerization domain linking the two motor domains ("heads"). In this study, the share of load directly born by each head is calculated, allowing for an unambiguous estimation of load effects on the ATP turnover and random diffusion of individual heads. The results show that the load modulations of ATP turnover and head diffusion are both essential in determining the performance of the dimer under loads. It is found that the consecutive run length of the dimer critically depends upon a few pathways, leading to the detachment of individual heads from MT. Modifying rates for these detachment pathways changes the run length but not the velocity of the dimer, consistent with mutant experiments. The run length may increase with or without the ATP concentration, depending upon a single rate for pure mechanical detachment. This finding provides an explanation to a previous controversy concerning ATP dependence of the run length, and related quantitative predictions of this study can be tested by a future experiment. This study also finds that the experimental observations for assisting loads can be quantitatively explained by load-biased head diffusion. We thus conclude that the dimer motility under resisting as well as assisting loads is governed by essentially the same mechanisms.
Fan
Dagong
D
Institute of Modern Physics, and Applied Ion Beam Physics Laboratory, Fudan University, Shanghai, China.
Zheng
Wenwei
W
Hou
Ruizheng
R
Li
Fuli
F
Wang
Zhisong
Z
D000255:Adenosine Triphosphate / Q000378:metabolism; D004058:Diffusion; D019281:Dimerization; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D012996:Solutions; D014783:Viscosity
D012996:Solutions; D000255:Adenosine Triphosphate; D016547:Kinesins