A comparative study of motor-protein motions by using a simple elastic-network model - PubMed (original) (raw)

Comparative Study

. 2003 Nov 11;100(23):13253-8.

doi: 10.1073/pnas.2235686100. Epub 2003 Oct 29.

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Comparative Study

A comparative study of motor-protein motions by using a simple elastic-network model

Wenjun Zheng et al. Proc Natl Acad Sci U S A. 2003.

Abstract

In this work, we report on a study of the structure-function relationships for three families of motor proteins, including kinesins, myosins, and F1-ATPases, by using a version of the simple elastic-network model of large-scale protein motions originally proposed by Tirion [Tirion, M. (1996) Phys. Rev. Lett. 77, 1905-1908]. We find a surprising dichotomy between kinesins and the other motor proteins (myosins and F1-ATPase). For the latter, there exist one or two dominant lowest-frequency modes (one for myosin, two for F1-ATPase) obtained from normal-mode analysis of the elastic-network model, which overlap remarkably well with the measured conformational changes derived from pairs of solved crystal structures in different states. Furthermore, we find that the computed global conformational changes induced by the measured deformation of the nucleotide-binding pocket also overlap well with the measured conformational changes, which is consistent with the "nucleotide-binding-induced power-stroke" scenario. In contrast, for kinesins, this simplicity breaks down. Multiple modes are needed to generate the measured conformational changes, and the computed displacements induced by deforming the nucleotide-binding pocket also overlap poorly with the measured conformational changes, and are insufficient to explain the large-scale motion of the relay helix and the linker region. This finding may suggest the presence of two different mechanisms for myosins and kinesins, despite their strong evolutionary ties and structural similarities.

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Figures

Fig. 1.

Fig. 1.

The overlap of the measured conformational change with the lowest 50 normal modes for myosins and ATPases: myosin 1KK8 (with truncated lever) to 1KK7 (a); 1KK8 (with truncated lever) to 1DFL (b); and F1-ATPase PDB ID code 1H8H (chain E) to PDB ID code1H8E (chain E) (c). The thick curve is the overlap per mode, and the thin curve is the cumulative overlap using all modes below a given mode. It is observed that there exists a single mode that dominates the measured conformational change in all three cases.

Fig. 2.

Fig. 2.

The amplitude of the computed displacement induced by the pocket deformation versus the measured conformational change for myosin 1KK8 (with truncated lever) to 1KK7 (a) myosin 1KK8 (with truncated lever); to 1DFL (b); and F1-ATPase 1H8H chain E to 1H8E chain E (c). Thick curve, amplitude of the measured conformational change; thin dotted curve, amplitude of the displacement induced by the nucleotide binding pocket deformation; boxes, nucleotide-binding sites.

Fig. 3.

Fig. 3.

The overlap of the measured conformational change with the lowest 50 normal modes for kinesins:1I6I to 1I5S (a) and 1MKJ to 1BG2 (b). Thick curve, overlap per mode; thin curve, cumulative overlap using all modes below a given mode. It is observed that there does not exist a single mode that dominates the measured conformational change.

Fig. 4.

Fig. 4.

The amplitude of the computed displacement induced by the pocket deformation versus the measured conformational change for kinesins: 1I6I to 1I5S (a) and 1MKJ to 1BG2 (b). Thick lines, amplitude of the measured conformational change; thin dotted lines, amplitude of the displacement induced by the nucleotide-binding pocket deformation; boxes, nucleotide-binding sites.

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References

    1. Vale, R. & Milligan, R. (2000) Science 288, 88-95. - PubMed
    1. Himmel, D., Gourinath, S., Reshetnikova, L., Shen, Y., Szent-Gyorgyi, A. & Cohen, C. (2002) Proc. Natl. Acad. Sci. USA 99, 12645-12650. - PMC - PubMed
    1. Cordova, N. J., Ermentrout, B. & Oster, G. F. (1992) Proc. Natl. Acad. Sci. USA 89, 339-343. - PMC - PubMed
    1. Wriggers, W. & Schulten, K. (1998) Biophys. J. 75, 646-661. - PMC - PubMed
    1. Xing, J., Wriggers, W., Jefferson, G. M., Stein, R., Cheung, H. C. & Rosenfeld, S. S. (2000) J. Biol. Chem. 275, 35413-35423. - PubMed

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