LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Publisher: Wiley
Languages: English
Types: Article
Subjects:
Advances in structural biology, such as cryo-electron microscopy (cryo-EM) have allowed for a number of sophisticated protein complexes to be characterized. However, often only a static snapshot of a protein complex is visualized despite the fact that conformational change is frequently inherent to biological function, as is the case for molecular motors. Computer simulations provide valuable insights into the different conformations available to a particular system that are not accessible using conventional structural techniques. For larger proteins and protein complexes, where a fully atomistic description would be computationally prohibitive, coarse-grained simulation techniques such as Elastic Network Modeling (ENM) are often employed, whereby each atom or group of atoms is linked by a set of springs whose properties can be customized according to the system of interest. Here we compare ENM with a recently proposed continuum model known as Fluctuating Finite Element Analysis (FFEA), which represents the biomolecule as a viscoelastic solid subject to thermal fluctuations. These two complementary computational techniques are used to answer a critical question in the rotary ATPase family; implicit within these motors is the need for a rotor axle and proton pump to rotate freely of the motor domain and stator structures. However, current single particle cryo-EM reconstructions have shown an apparent connection between the stators and rotor axle or pump region, hindering rotation. Both modeling approaches show a possible role for this connection and how it would significantly constrain the mobility of the rotary ATPase family.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Muench SP, Trinick J, Harrison MA. Structural divergence of the rotary ATPases. Q Rev Biophys 2011;44:311-356.
    • 2. Imamura H, Nakano M, Noji H, Muneyuki E, Ohkuma S, Yoshida M, Yokoyama K. Evidence for rotation of V1-ATPase. Proc Natl Acad Sci USA 2003;100:2312-2315.
    • 3. Noji H, Yasuda R, Yoshida M, Kinosita K, Jr. Direct observation of the rotation of F1-ATPase. Nature 1997;386:299-302.
    • 4. Boyer PD. The ATP synthase-a splendid molecular machine. Annu Rev Biochem 1997;66:717-749.
    • 5. Sambongi Y, Iko Y, Tanabe M, Omote H, Iwamoto-Kihara A, Ueda I, Yanagida T, Wada Y, Futai M. Mechanical rotation of the c subunit oligomer in ATP synthase (F0F1): direct observation. Science 1999;286:1722-1724.
    • 6. Yokoyama K, Nakano M, Imamura H, Yoshida M, Tamakoshi M. Rotation of the proteolipid ring in the V-ATPase. J Biol Chem 2003;278:24255-24258.
    • 7. Mitome N, Suzuki T, Hayashi S, Yoshida M. Thermophilic ATP synthase has a decamer c-ring: indication of noninteger 10:3 H1/ATP ratio and permissive elastic coupling. Proc Natl Acad Sci USA 2004; 101:12159-12164.
    • 8. Pogoryelov D, Reichen C, Klyszejko AL, Brunisholz R, Muller DJ, Dimroth P, Meier T. The oligomeric state of c rings from cyanobacterial F-ATP synthases varies from 13 to 15. J Bacteriol 2007;189:5895-5902.
    • 9. Vollmar M, Schlieper D, Winn M, Buchner C, Groth G. Structure of the c(14) rotor ring of the proton translocating chloroplast ATP synthase. J Biol Chem 2009;284:18228-18235.
    • 10. Meier T, Polzer P, Diederichs K, Welte W, Dimroth P. Structure of the rotor ring of F-type Na1-ATPase from Ilyobacter tartaricus. Science 2005;308:659-662.
    • 11. Pogoryelov D, Yu J, Meier T, Vonck J, Dimroth P, Muller DJ. The c15 ring of the Spirulina platensis F-ATP synthase: F1/F0 symmetry mismatch is not obligatory. EMBO Rep 2005;6:1040-1044.
    • 12. Cherepanov DA, Mulkidjanian AY, Junge W. Transient accumulation of elastic energy in proton translocating ATP synthase. FEBS Lett 1999;449:1-6.
    • 13. Grabe M, Wang H, Oster G. The mechanochemistry of V-ATPase proton pumps. Biophys J 2000;78:2798-813.
    • 14. Junge W, Sielaff H, Engelbrecht S. Torque generation and elastic power transmission in the rotary F(O)F(1)-ATPase. Nature 2009;459:364-370.
    • 15. Sielaff H, Rennekamp H, Wachter A, Xie H, Hilbers F, Feldbauer K, Dunn SD, Engelbrecht S, Junge W. Domain compliance and elastic power transmission in rotary F(O)F(1)-ATPase. Proc Natl Acad Sci USA 2008;105:17760-17765.
    • 16. Wachter A, Bi Y, Dunn SD, Cain BD, Sielaff H, Wintermann F, Engelbrecht S, Junge W. Two rotary motors in F-ATP synthase are elastically coupled by a flexible rotor and a stiff stator stalk. Proc Natl Acad Sci USA 2011;108:3924-3929.
    • 17. Balakrishna AM, Hunke C, Gruber G. The structure of subunit E of the Pyrococcus horikoshii OT3 A-ATP synthase gives insight into the elasticity of the peripheral stalk. J Mol Biol 2012;420:155-163.
    • 18. Bernal RA, Stock D. Three-dimensional structure of the intact Thermus thermophilus H1-ATPase/synthase by electron microscopy. Structure 2004;12:1789-98.
    • 19. Bottcher B, Bertsche I, Reuter R, Graber P. Direct visualisation of conformational changes in EF(0)F(1) by electron microscopy. J Mol Biol 2000;296:449-457.
    • 20. Matthies D, Haberstock S, Joos F, Dotsch V, Vonck J, Bernhard F, Meier T. Cell-free expression and assembly of ATP synthase. J Mol Biol 2011;413:593-603.
    • 21. Stewart AG, Lee LK, Donohoe M, Chaston JJ, Stock D. The dynamic stator stalk of rotary ATPases. Nat Commun 2012;3:687.
    • 22. Song CF, Papachristos K, Rawson S, Huss M, Wieczorek H, Paci E, Trinick J, Harrison MA, Muench SP. Flexibility within the Rotor and Stators of the Vacuolar H1-ATPase. PLOS ONE 2013;8(12).
    • 23. Tirion MM. Large amplitude elastic motions in proteins from a single-parameter, atomic analysis. Phys Rev Lett 1996;77:1905-1908.
    • 24. Chacon P, Tama F, Wriggers W. Mega-Dalton biomolecular motion captured from electron microscopy reconstructions. J Mol Biol 2003;326:485-492.
    • 25. Tama F, Wriggers W, Brooks CL, III. Exploring global distortions of biological macromolecules and assemblies from low-resolution structural information and elastic network theory. J Mol Biol 2002; 321:297-305.
    • 26. Oliver RC, Read DJ, Harlen OG, Harris SA. A stochastic finite element model for the dynamics of globular macromolecules. J Comp Phys 2013;239:147-165.
    • 27. Scho€berl J. NETGEN - an advancing front 2d/3d-mesh generator based on abstract rules. Computing and visualization in science 1997;1:41-52.
    • 28. Radmacher M, Fritz M, Cleveland JP, Walters DA, Hansma PK. Imaging adhesion forces and elasticity of lysozyme adsorbed on mica with the atomic force microscope. Langmuir 1994;10:3809- 3814.
    • 29. Fischer H, Polikarpov I, Craievich AF. Average protein density is a molecular weight dependent function. Protein Science 2004;13: 2825-2828.
    • 30. Quillin ML, Matthews BW. Accurate calculation of the density of proteins. Acta Crystallogr Sect D: Biol Crystallogr 2000;56:791-794.
    • 31. Wriggers W, Milligan RA, Schulten K, McCammon JA. Self-organizing neural networks bridge the biomolecular resolution gap. J Mol Biol 1998;284:1247-1254.
    • 32. Stember JN, Wriggers W. Bend-twist-stretch model for coarse elastic network simulation of biomolecular motion. J Chem Phys 2009;131: 074112.
    • 33. Meyer T, Ferrer-Costa C, Perez A, Rueda M, Bidon-Chanal A, Luque FJ, Laughton CA, Orozco M. Essential dynamics: A tool for efficient trajectory compression and management. J Chem Theory Comput 2006;2:251-258.
    • 34. Lau WCY, Rubinstein JL. Structure of intact Thermus thermophilus V-ATPase by cryo-EM reveals organization of the membrane-bound VO motor. Proc Natl Acad Sci USA 2010;107:1367-1372.
    • 35. Muench SP, Huss M, Song CF, Phillips C, Wieczorek H, Trinick J, Harrison MA. Cryo-electron microscopy of the vacuolar ATPase motor reveals its mechanical and regulatory complexity. J Mol Biol 2009;386:989-999.
    • 36. Benlekbir S, Bueler SA, Rubinstein JL. Structure of the vacuolartype ATPase from Saccharomyces cerevisiae at 11-angstrom resolution. Nat Struct Mol Biol 2012;19:1356.
    • 37. Lau WCY, Rubinstein JL. Subnanometre-resolution structure of the intact Thermus thermophilus H1-driven ATP synthase. Nature 2012; 481(7380):214.
    • 38. Kane PM. Disassembly and reassembly of the yeast vacuolar H(1)- ATPase in vivo. J Biol Chem 1995;270:17025-17032.
    • 39. Sumner JP, Dow JA, Earley FG, Klein U, Jager D, Wieczorek H. Regulation of plasma membrane V-ATPase activity by dissociation of peripheral subunits. J Biol Chem 1995;270:5649-5653.
    • 40. Muench SP, Scheres SH, Huss M, Phillips C, Vitavska O, Wieczorek H, Trinick J, Harrison MA. Subunit positioning and stator filament stiffness in regulation and power transmission in the V1 motor of the Manduca sexta V-ATPase. J Mol Biol 2014; 426:286-300.
    • 41. Tabke K, Albertmelcher A, Vitavska O, Huss M, Schmitz HP, Wieczorek H. Reversible disassembly of the yeast V-ATPase revisited under in vivo conditions. Biochem J 2014;462:185-197.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article