Myosin-V as a mechanical sensor: an elastic network study - PubMed (original) (raw)

Myosin-V as a mechanical sensor: an elastic network study

Markus Düttmann et al. Biophys J. 2012.

Abstract

According to recent experiments, the molecular-motor myosin behaves like a strain sensor, exhibiting different functional responses when loads in opposite directions are applied to its tail. Within an elastic-network model, we explore the sensitivity of the protein to the forces acting on the tail and find, in agreement with experiments, that such forces invoke conformational changes that should affect filament binding and ADP release. Furthermore, conformational responses of myosin to the application of forces to individual residues in its principal functional regions are systematically investigated and a detailed sensitivity map of myosin-V is thus obtained. The results suggest that the strain-sensor behavior is involved in the intrinsic operation of this molecular motor.

Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

Myosin-V (a) and its EN (b). In panel a, three principal functional regions of the protein are schematically shown; the ATP-analog is also displayed (orange). Moreover, some important structural elements, such as the front and the back doors and the HCM loop, are also indicated here. In panel b, each particle corresponds to a residue, the links represent elastic interactions between them.

Figure 2

Figure 2

(a) Set of residues probed by application of static forces. (b) Labels, and the distances between them, used to monitor conformational changes.

Figure 3

Figure 3

Responses of pair distances between labels 115 and 297 (black), 219 and 442 (red), 343 and 517 (blue), and 386 and 517 (green) as functions of the amplitude of the force applied to the tail. Small abrupt changes observed at large negative forces are due to local buckling effects.

Figure 4

Figure 4

Sensitivity of residues in the NBP region. Directions of communication are indicated by colored arrows. (Inset) Enlargement of the region of the NBP outlined by the box. Residues most sensitive with respect to tail motion and conformational changes in the actin cleft are colored red. Responses induced by the forces applied at the gray colored residues are weaker.

Figure 5

Figure 5

Changes in the distance between residues 343 and 517, which characterize opening of the actin-binding cleft, as functions of the force applied to residue 442 in the back-door region. The red curve corresponds to the forward force of 5 Å applied to the tail. The green curve is for the force with the same strength applied in the backward direction. The blue curve corresponds to the absence of force.

Figure 6

Figure 6

Responses induced by the application of forces to residues in the actin-binding cleft region. Red spheres indicate residues 377–390 in the HCM loop, 340–350 in the upper 50-kDa subdomain, and 540–544 in the lower 50-kDa subdomain. Gray spheres represent less sensitive residues in the lower 50-kDa subdomain. Arrows schematically indicate the directions and strength of intramolecular communication.

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References

    1. Sellers J.R. 2nd ed. Oxford University Press; New York: 1999. Myosins.
    1. Sweeney H.L., Houdusse A. Structural and functional insights into the myosin motor mechanism. Annu. Rev. Biophys. 2010;39:539–557. - PubMed
    1. Iwaki M., Iwane A.H., Yanagida T. Brownian search-and-catch mechanism for myosin-VI steps. Nat. Chem. Biol. 2009;5:403–405. - PubMed
    1. Oguchi Y., Mikhailenko S.V., Ishiwata S. Robust processivity of myosin V under off-axis loads. Nat. Chem. Biol. 2010;6:300–305. - PMC - PubMed
    1. Oguchi Y., Mikhailenko S.V., Ishiwata S. Load-dependent ADP binding to myosins V and VI: implications for subunit coordination and function. Proc. Natl. Acad. Sci. USA. 2008;105:7714–7719. - PMC - PubMed

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