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Computer Simulation of Assembly and Co-operativity of Hexameric AAA ATPases

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  • Doan Tuong-Van Le
  • Thomas Eckert
  • Günther Woehlke

Abstract

AAA ATPases form a functionally diverse superfamily of proteins. Most members form homo-hexameric ring complexes, are catalytically active only in the fully assembled state, and show co-operativity among the six subunits. The mutual dependence among the subunits is clearly evidenced by the fact that incorporation of mutated, inactive subunits can decrease the activity of the remaining wild type subunits. For the first time, we develop here models to describe this form of allostery, evaluate them in a simulation study, and test them on experimental data. We show that it is important to consider the assembly reactions in the kinetic model, and to define a formal inhibition scheme. We simulate three inhibition scenarios explicitly, and demonstrate that they result in differing outcomes. Finally, we deduce fitting formulas, and test them on real and simulated data. A non-competitive inhibition formula fitted experimental and simulated data best. To our knowledge, our study is the first one that derives and tests formal allosteric schemes to explain the inhibitory effects of mutant subunits on oligomeric enzymes.

Suggested Citation

  • Doan Tuong-Van Le & Thomas Eckert & Günther Woehlke, 2013. "Computer Simulation of Assembly and Co-operativity of Hexameric AAA ATPases," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-19, July.
  • Handle: RePEc:plo:pone00:0067815
    DOI: 10.1371/journal.pone.0067815
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    References listed on IDEAS

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    1. Elio A. Abbondanzieri & Xiaowei Zhuang, 2009. "Concealed enzyme coordination," Nature, Nature, vol. 457(7228), pages 392-393, January.
    2. Antonina Roll-Mecak & Ronald D. Vale, 2008. "Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin," Nature, Nature, vol. 451(7176), pages 363-367, January.
    3. Sarah Rice & Abel W. Lin & Daniel Safer & Cynthia L. Hart & Nariman Naber & Bridget O. Carragher & Shane M. Cain & Elena Pechatnikova & Elizabeth M. Wilson-Kubalek & Michael Whittaker & Edward Pate & , 1999. "A structural change in the kinesin motor protein that drives motility," Nature, Nature, vol. 402(6763), pages 778-784, December.
    4. Andreas Martin & Tania A. Baker & Robert T. Sauer, 2005. "Rebuilt AAA + motors reveal operating principles for ATP-fuelled machines," Nature, Nature, vol. 437(7062), pages 1115-1120, October.
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