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Control of a biomolecular motor-powered nanodevice with an engineered chemical switch

Nature Materials volume 1, pages 173–177 (2002)Cite this article

Abstract

The biophysical and biochemical properties of motor proteins have been well-studied, but these motors also show promise as mechanical components in hybrid nano-engineered systems1,2,3,4. The cytoplasmic F1 fragment of the adenosine triphosphate synthase (F1-ATPase) can function as an ATP-fuelled rotary motor4,5,6,7 and has been integrated into self-assembled nanomechanical systems as a mechanical actuator4,8. Here we present the rational design, construction and analysis of a mutant F1-ATPase motor containing a metal-binding site that functions as a zinc-dependent, reversible on/off switch. Repeated cycles of zinc addition and removal by chelation result in inhibition and restoration, respectively, of both ATP hydrolysis and motor rotation of the mutant, but not of the wild-type F1 fragment. These results demonstrate the ability to engineer chemical regulation into a biomolecular motor and represent a critical step towards controlling integrated nanomechanical devices at the single-molecule level.

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Figure 1: Molecular model of the computationally designed Zn2+ binding site in the bovine F1-ATPase.
Figure 2: Steady-state kinetics of ATP hydrolysis in the wild-type and mutant TF1 enzymes.
Figure 3: Measurements of single-molecule rotation and control.

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References

  1. Hess, H., Clemmens, J., Qin, D., Howard, J. & Vogel, V. Light-controlled molecular shuttles made from motor proteins carrying cargo on engineered surfaces. Nanoletters 1, 235–239 (2001).

    Article  CAS  Google Scholar 

  2. Bohm, K.J., Stracke, R., Muhlig, P. & Unger, E. Motor protein-driven unidirectional transport of micrometer-sized cargoes across isopolar microtubule arrays. Nanotechnology 12, 238–244 (2001).

    Article  CAS  Google Scholar 

  3. Hiratsuka, Y., Tada, T., Oiwa, K., Kanayama, T. & Uyeda, T. Controlling the direction of kinesin-driven microtubule movements along microlithographic tracks. Biophys. J. 81, 1555–1561 (2001).

    Article  CAS  Google Scholar 

  4. Soong, R.K. et al. Powering an inorganic nanodevice with a biomolecular motor. Science 290, 1555–1558 (2000).

    Article  CAS  Google Scholar 

  5. Noji, H., Yasuda, R., Yoshida, M. & Kinosita, K. Direct observation of the rotation of F1-ATPase. Nature 386, 299–302 (1997).

    Article  CAS  Google Scholar 

  6. Yasuda, R., Noji, H., Kinosita, K. & Yoshida, M. F1-ATPase is a highly efficient molecular motor that rotates with discrete 120 degrees steps. Cell 93, 1117–1124 (1998).

    Article  CAS  Google Scholar 

  7. Yasuda, R., Noji, H., Yoshida, M., Kinosita, K. & Itoh, H. Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase. Nature 410, 898–904 (2001).

    Article  CAS  Google Scholar 

  8. Soong, R.K., Neves, H.P., Bachand, G.D., Schmidt, J. & Montemagno, C.D. Engineering hybrid nanoscale devices powered by biomolecular motors. Biomed. Microdevices 3, 71–73 (2001).

    Article  CAS  Google Scholar 

  9. Abrahams, P., Leslie, A.G.W., Lutter, R. & Walker, J.E. Structure at 2.8 Å resolution of F1-ATPase from bovine heart mitochondria. Nature 370, 621–628 (1994).

    Article  CAS  Google Scholar 

  10. Perutz, M.F. Mechanism of cooperativity and allosteric regulation in proteins. Q. Rev. Biophys. 22, 139–237 (1989).

    Article  CAS  Google Scholar 

  11. Glusker, J.P. Structural aspects of metal liganding to functional groups in proteins. Adv. Prot. Chem. 42, 1–76 (1991).

    CAS  Google Scholar 

  12. Hellinga, H.W. & Richards, F.M. Construction of new ligand-binding sites in proteins of known structure. 1. Computer-aided modeling of sites with predefined geometry. J. Mol. Biol. 222, 763–785 (1991).

    Article  CAS  Google Scholar 

  13. Marvin, J.S. & Hellinga, H.W. Conversion of a maltose receptor into a zinc biosensor by computational design. Proc. Natl Acad. Sci. USA 98, 4955–4960 (2001).

    Article  CAS  Google Scholar 

  14. Benson, D., Haddy, A.E. & Hellinga, H.W. Converting a maltose receptor into a nascent binuclear copper oxygenase by computational design. Biochemistry 41, 3262–3269 (2002).

    Article  CAS  Google Scholar 

  15. Marvin, J. et al. The rational design of allosteric interactions in a monomeric protein and its applications to the construction of biosensors. Proc. Natl Acad. Sci. USA 98, 4366–4371 (1997).

    Article  Google Scholar 

  16. Shirakihara, Y. et al. The crystal structure of the nucleotide-free subcomplex of F1-ATPase from the thermophilic Bacillus PS3 is a symmetric trimer. Structure 5, 825–836 (1997).

    Article  CAS  Google Scholar 

  17. Bachand, G.D. & Montemagno, C.D. Constructing organic/inorganic NEMS devices powered by biomolecular motors. Biomed. Microdevices 2, 179–184 (2000).

    Article  CAS  Google Scholar 

  18. Pullman, M.E., Penefsky, H.S., Datta, A. & Racker, E. Partial resolution of the enzyme catalyzing oxidative phosphorylation. I. Purification and properties of soluble, dinitrophenol-stimulated adenosine triphosphatase. J. Biol. Chem. 235, 3322–3329 (1960).

    CAS  Google Scholar 

  19. Segel, I.H. Enzyme Kinetics (Wiley, New York, 1975).

    Google Scholar 

  20. Hunt, A.J., Gittes, F. & Howard, J. The force exerted by a single kinesin molecule against a viscous load. Biophys. J. 67, 766–781 (1994).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank C. Xu for help in the protein modelling of the TF1 structure. This research was supported in part by grants from NASA (NAG5-8775), DARPA (N00014-99-1-0436) and NSF (ECS-0084732). Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the US Department of Energy under contract DE-AC04-94AL85000.

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  1. Shahir S. Rizk, Loren L. Looger & Homme W. Hellinga

    Present address: Department of Biochemistry, Box 3711, Duke University Medical Center, Durham, 27710, North Carolina, USA

  2. George D. Bachand

    Present address: Biomolecular Materials and Interfaces, Sandia National Laboratories, PO Box 5800, MS 1413, Albuquerque, New Mexico, 87185-1413, USA

Authors and Affiliations

  1. Department of Bioengineering, University of California, Los Angeles, 90095, California, USA

    Haiqing Liu, Jacob J. Schmidt & Carlo D. Montemagno

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  1. Haiqing Liu
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Correspondence to Carlo D. Montemagno.

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Liu, H., Schmidt, J., Bachand, G. et al. Control of a biomolecular motor-powered nanodevice with an engineered chemical switch. Nature Mater 1, 173–177 (2002). https://doi.org/10.1038/nmat761

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