Nucleotide-Dependent Single- to Double-Headed Binding of Kinesin

Kawaguchi, Kenji; Ishiwata, Shin’ichi

doi:10.1126/science.291.5504.667

Cited by 117 publications

(106 citation statements)

References 26 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These values are close enough to claim that the stall force in our model does not depend on the ATP concentration sensitively. The corresponding stall force in real dimension is about 6 pN, which is comparable with the experimental value of 6-7 pN [16,21,29]. When the load is less than 4 pN, the average velocity does not depend on the load, but does depend on the ATP concentration.…”

Section: Results Of Numerical Simulationssupporting

confidence: 68%

“…Conventional kinesin, kinesin-1, walks processively along a microtubule toward the plus end (defined as 'forward') [13][14][15] generating 6-8 pN per step [16] by consuming one adenosine-triphosphate (ATP) [17,18] and transports vesicles and organelles [19][20][21][22][23][24][25][26][27][28]. One of the interesting observations is the backward moonwalking of kinesin [25,26,[28][29][30][31][32][33][34] under a backward load much larger than the stall force.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Walking motion of an overdamped active particle in a ratchet potential

2011

View full text Add to dashboard Cite

An active particle can convert its internal energy into mechanical work. We study a generalized energy-depot model of an overdamped active particle in a ratchet potential. Using well-known biological parameters for kinesin-1 and modeling ATP influx as a pulsed energy supply, we apply our model to the molecular motor system. We find that our simple model can capture the essential properties of the kinesin motor such as forward stepping, stalling, backward stepping, dependence on ATP concentration, and stall force. Our model might be quite universal in the sense that it is able to describe dynamics of various types of motors as long as realistic parameters for each motor species are adopted.

show abstract

Section: Results Of Numerical Simulationssupporting

confidence: 68%

mentioning

confidence: 99%

Walking motion of an overdamped active particle in a ratchet potential

2011

View full text Add to dashboard Cite

show abstract

“…These results and our data on the kinesin-microtubule interaction (21,30) strongly suggest that the intramolecular load that arises from double-headed binding of a motor to the lattice track is a major regulator of the mechanochemical kinetics, which coordinates the enzymatic cycles in the two heads and controls the unidirectional stepping of dimeric ATP-driven processive motors, regardless of whether the lattice is an actin filament or a microtubule. However, the different characteristics of load dependence of ADP binding/dissociation kinetics between myosins V and VI suggest that this regulatory mechanism is adapted to the particular cellular functions of each molecular motor.…”

Section: Adpboundmentioning

confidence: 52%

Load-dependent ADP binding to myosins V and VI: Implications for subunit coordination and function

Oguchi

Mikhailenko

Ohki

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

112

View full text Add to dashboard Cite

show abstract

“…Moreover, complexes of kinesin with MTs generate identical EPR spectra in the presence of AMP-PNP or ADP⅐BeF x (40). The evidence indicates that the binding of AMP-PNP docks the neck linker (12,23,(41)(42)(43)(44), favoring a two-heads-bound configuration, with AMP-PNP present on the rear head and no nucleotide on the front head. We therefore anticipate that the binding of BeF x to kinesin induces a similar two-heads-bound state, but with ADP⅐BeF x bound to the rear head.…”

mentioning

confidence: 71%

Backsteps induced by nucleotide analogs suggest the front head of kinesin is gated by strain

Guydosh

Block

2006

Proc. Natl. Acad. Sci. U.S.A.

128

156

View full text Add to dashboard Cite

The two-headed kinesin motor harnesses the energy of ATP hydrolysis to take 8-nm steps, walking processively along a microtubule, alternately stepping with each of its catalytic heads in a hand-over-hand fashion. Two persistent challenges for models of kinesin motility are to explain how the two heads are coordinated (''gated'') and when the translocation step occurs relative to other events in the mechanochemical reaction cycle. To investigate these questions, we used a precision optical trap to measure the singlemolecule kinetics of kinesin in the presence of substrate analogs beryllium fluoride or adenylyl-imidodiphosphate. We found that normal stepping patterns were interspersed with long pauses induced by analog binding, and that these pauses were interrupted by short-lived backsteps. After a pause, processive stepping could only resume once the kinesin molecule took an obligatory, terminal backstep, exchanging the positions of its front and rear heads, presumably to allow release of the bound analog from the new front head. Preferential release from the front head implies that the kinetics of the two heads are differentially affected when both are bound to the microtubule, presumably by internal strain that is responsible for the gating. Furthermore, we found that ATP binding was required to reinitiate processive stepping after the terminal backstep. Together, our results support stepping models in which ATP binding triggers the mechanical step and the front head is gated by strain.motor coordination ͉ optical tweezers ͉ single-molecule biophysics ͉ gating ͉ processivity C onventional kinesin, the founding member of the Kinesin-1 family, uses energy from ATP hydrolysis to transport cellular cargo, taking 8-nm steps along microtubules (MTs) (1). Kinesin molecules are formed from two identical heavy chains, whose N-terminal regions fold to form catalytic motor domains, or heads, which are joined by ''neck-linker'' regions to a common, coiled-coil stalk. With each step, the two kinesin heads exchange leading and trailing positions as they alternately hydrolyze ATP, generating ''hand-over-hand'' motion (2-7). This motion is processive under moderate loads for up to Ϸ100 steps in succession, a property that enables small numbers of motors to ferry cargo over long distances (8, 9). The mechanism responsible for the remarkable processivity of kinesin remains unresolved. Furthermore, the relative order of the translocation step with respect to other steps in the mechanochemical cycle is not established.A corollary of kinesin processivity is that its two heads do not function independently, but in concert. Put another way, the relative phase between the heads must be synchronized by a gating mechanism that prevents both heads from dissociating simultaneously from the MT. Because of the 2-fold symmetry imparted by the kinesin structure, this mechanism must break symmetry to permit synchronization. The most attractive candidate for such a mechanism is the mechanical strain that develops when the two heads separate an...

show abstract

Nucleotide-Dependent Single- to Double-Headed Binding of Kinesin

Cited by 117 publications

References 26 publications

Walking motion of an overdamped active particle in a ratchet potential

Walking motion of an overdamped active particle in a ratchet potential

Load-dependent ADP binding to myosins V and VI: Implications for subunit coordination and function

Backsteps induced by nucleotide analogs suggest the front head of kinesin is gated by strain

Contact Info

Product

Resources

About