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The nature of the globular- to fibrous-actin transition

Nature volume 457, pages 441–445 (2009)Cite this article

A Corrigendum to this article was published on 24 September 2009

Abstract

Actin plays crucial parts in cell motility through a dynamic process driven by polymerization and depolymerization, that is, the globular (G) to fibrous (F) actin transition. Although our knowledge about the actin-based cellular functions and the molecules that regulate the G- to F-actin transition is growing, the structural aspects of the transition remain enigmatic. We created a model of F-actin using X-ray fibre diffraction intensities obtained from well oriented sols of rabbit skeletal muscle F-actin to 3.3 Å in the radial direction and 5.6 Å along the equator. Here we show that the G- to F-actin conformational transition is a simple relative rotation of the two major domains by about 20 degrees. As a result of the domain rotation, the actin molecule in the filament is flat. The flat form is essential for the formation of stable, helical F-actin. Our F-actin structure model provides the basis for understanding actin polymerization as well as its molecular interactions with actin-binding proteins.

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Figure 1: Comparison between the observed (right half) and calculated (left half) diffraction patterns from our model.
Figure 2: Transition from the G-actin conformation to the flat conformation in F-actin.
Figure 3: Intra- and inter-strand contacts within our F-actin model.
Figure 4: Comparison between the two-stranded straight polymer in the actin–formin crystal and our helical F-actin polymer.

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Protein Data Bank

Data deposits

The coordinates for F-actin model have been submitted to PDB under accession number 2ZWH.

References

  1. Straub, F. B. in Studies Int med Chem Univ Szeged (ed Szent-Györgi) 2, 3–15 (Karger, 1942)

    Google Scholar 

  2. Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003)

    Article  CAS  Google Scholar 

  3. Carlier, M. F. & Pantaloni, D. Control of actin assembly dynamics in cell motility. J. Biol. Chem. 282, 23005–23009 (2007)

    Article  CAS  Google Scholar 

  4. Oosawa, F. & Asakura, S. Thernodynamics of the Polymerization of Protein (Academic, 1975)

    Google Scholar 

  5. Wegner, A. Head to tail polymerization of actin. J. Mol. Biol. 108, 139–150 (1976)

    Article  CAS  Google Scholar 

  6. Kabsch, W. et al. Atomic structure of the actin:DNase I complex. Nature 347, 37–44 (1990)

    Article  ADS  CAS  Google Scholar 

  7. Holmes, K. C., Popp, D., Gebhard, W. & Kabsch, W. Atomic model of the actin filament. Nature 347, 44–49 (1990)

    Article  ADS  CAS  Google Scholar 

  8. Lorenz, M., Popp, D. & Holmes, K. C. Refinement of the F-actin model against X-ray fiber diffraction data by the use of a directed mutation algorithm. J. Mol. Biol. 234, 826–836 (1993)

    Article  CAS  Google Scholar 

  9. Tirion, M. M., ben-Avraham, D., Lorenz, M. & Holmes, K. C. Normal modes as refinement parameters for the F-actin model. Biophys. J. 68, 5–12 (1995)

    Article  ADS  CAS  Google Scholar 

  10. Holmes, K. C. et al. Electron cryo-microscopy shows how strong binding of myosin to actin releases nucleotide. Nature 425, 423–427 (2003)

    Article  ADS  CAS  Google Scholar 

  11. Wu, Y. & Ma, J. Refinement of F-actin model against fiber diffraction data by long-range normal modes. Biophys. J. 86, 116–124 (2004)

    Article  ADS  CAS  Google Scholar 

  12. Oda, T. et al. Modeling of the F-actin structure. Adv. Exp. Med. Biol. 592, 385–401 (2007)

    Article  Google Scholar 

  13. van den Ent, F., Amos, L. A. & Löwe, J. Prokaryotic origin of the actin cytoskeleton. Nature 413, 39–44 (2001)

    Article  ADS  CAS  Google Scholar 

  14. Joel, P. B., Fagnant, P. M. & Trybus, K. M. Expression of a nonpolymerizable actin mutant in Sf9 cells. Biochemistry 43, 11554–11559 (2004)

    Article  CAS  Google Scholar 

  15. Wertman, K. F., Drubin, D. G. & Botstein, D. Systematic mutational analysis of the yeast ACT1 gene. Genetics 132, 337–350 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Allingham, J. S., Klenchin, V. A. & Rayment, I. Actin-targeting natural products: structures, properties and mechanisms of action. Cell. Mol. Life Sci. 63, 2119–2134 (2006)

    Article  CAS  Google Scholar 

  17. Morton, W. M., Ayscough, K. R. & McLaughlin, P. J. Latrunculin alters the actin–monomer subunit interface to prevent polymerization. Nature Cell Biol. 2, 376–378 (2000)

    Article  CAS  Google Scholar 

  18. Oda, T. et al. Effect of the length and effective diameter of F-actin on the filament orientation in liquid crystalline sols measured by x-ray fiber diffraction. Biophys. J. 75, 2672–2681 (1998)

    Article  ADS  CAS  Google Scholar 

  19. Hayward, S. & Berendsen, H. J. Systematic analysis of domain motions in proteins from conformational change: new results on citrate synthase and T4 lysozyme. Proteins 30, 144–154 (1998)

    Article  CAS  Google Scholar 

  20. Otterbein, L. R., Graceffa, P. & Dominguez, R. The crystal structure of uncomplexed actin in the ADP state. Science 293, 708–711 (2001)

    Article  CAS  Google Scholar 

  21. Michie, K. A. & Löwe, J. Dynamic filaments of the bacterial cytoskeleton. Annu. Rev. Biochem. 75, 467–492 (2006)

    Article  CAS  Google Scholar 

  22. Carballido-Lopez, R. The bacterial actin-like cytoskeleton. Microbiol. Mol. Biol. Rev. 70, 888–909 (2006)

    Article  CAS  Google Scholar 

  23. Chen, X., Cook, R. K. & Rubenstein, P. A. Yeast actin with a mutation in the “hydrophobic plug” between subdomains 3 and 4 (L266D) displays a cold-sensitive polymerization defect. J. Cell Biol. 123, 1185–1195 (1993)

    Article  CAS  Google Scholar 

  24. Volkmann, N. et al. The structural basis of myosin V processive movement as revealed by electron cryomicroscopy. Mol. Cell 19, 595–605 (2005)

    Article  CAS  Google Scholar 

  25. Rould, M. A. et al. Crystal structures of expressed non-polymerizable monomeric actin in the ADP and ATP states. J. Biol. Chem. 281, 31909–31919 (2006)

    Article  CAS  Google Scholar 

  26. Nolen, B. J. & Pollard, T. D. Insights into the influence of nucleotides on actin family proteins from seven structures of Arp2/3 complex. Mol. Cell 26, 449–457 (2007)

    Article  CAS  Google Scholar 

  27. Graceffa, P. & Dominguez, R. Crystal structure of monomeric actin in the ATP state. Structural basis of nucleotide-dependent actin dynamics. J. Biol. Chem. 278, 34172–34180 (2003)

    Article  CAS  Google Scholar 

  28. Robinson, R. C. et al. Crystal structure of Arp2/3 complex. Science 294, 1679–1684 (2001)

    Article  ADS  CAS  Google Scholar 

  29. De La Cruz, E. M. et al. Polymerization and structure of nucleotide-free actin filaments. J. Mol. Biol. 295, 517–526 (2000)

    Article  CAS  Google Scholar 

  30. Pollard, T. D. Regulation of actin filament assembly by Arp2/3 complex and formins. Annu. Rev. Biophys. Biomol. Struct. 36, 451–477 (2007)

    Article  CAS  Google Scholar 

  31. Iwasa, M. et al. Dual roles of Q137 of actin revealed by recombinant human cardiac muscle alpha -actin mutants. J. Biol. Chem. 283, 21045–21053 (2008)

    Article  CAS  Google Scholar 

  32. Vorobiev, S. et al. The structure of nonvertebrate actin: implications for the ATP hydrolytic mechanism. Proc. Natl Acad. Sci. USA 100, 5760–5765 (2003)

    Article  ADS  CAS  Google Scholar 

  33. Vogel, M., Bukau, B. & Mayer, M. P. Allosteric regulation of Hsp70 chaperones by a proline switch. Mol. Cell 21, 359–367 (2006)

    Article  CAS  Google Scholar 

  34. Yao, X., Nguyen, V., Wriggers, W. & Rubenstein, P. A. Regulation of yeast actin behavior by interaction of charged residues across the interdomain cleft. J. Biol. Chem. 277, 22875–22882 (2002)

    Article  CAS  Google Scholar 

  35. Nyman, T. et al. The role of MeH73 in actin polymerization and ATP hydrolysis. J. Mol. Biol. 317, 577–589 (2002)

    Article  CAS  Google Scholar 

  36. Otomo, T. et al. Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain. Nature 433, 488–494 (2005)

    Article  ADS  CAS  Google Scholar 

  37. Furuhashi, K. et al. Phosphorylation by actin kinase of the pointed end domain on the actin molecule. J. Biol. Chem. 267, 9326–9330 (1992)

    CAS  PubMed  Google Scholar 

  38. Klenchin, V. A., Khaitlina, S. Y. & Rayment, I. Crystal structure of polymerization-competent actin. J. Mol. Biol. 362, 140–150 (2006)

    Article  CAS  Google Scholar 

  39. Dalhaimer, P., Pollard, T. D. & Nolen, B. J. Nucleotide-mediated conformational changes of monomeric actin and Arp3 studied by molecular dynamics simulations. J. Mol. Biol. 376, 166–183 (2008)

    Article  CAS  Google Scholar 

  40. Ravelli, R. B. et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428, 198–202 (2004)

    Article  ADS  CAS  Google Scholar 

  41. Wang, H. W. & Nogales, E. Nucleotide-dependent bending flexibility of tubulin regulates microtubule assembly. Nature 435, 911–915 (2005)

    Article  ADS  CAS  Google Scholar 

  42. Wang, H. & Stubbs, G. Molecular dynamics in refinement against fiber diffraction data. Acta Crystallogr. A 49, 504–513 (1993)

    Article  CAS  Google Scholar 

  43. Narita, A. & Maeda, Y. Molecular determination by electron microscopy of the actin filament end structure. J. Mol. Biol. 365, 480–501 (2007)

    Article  CAS  Google Scholar 

  44. Narita, A., Takeda, S., Yamashita, A. & Maeda, Y. Structural basis of actin filament capping at the barbed-end: a cryo-electron microscopy study. EMBO J. 25, 5626–5633 (2006)

    Article  CAS  Google Scholar 

  45. Kraulis, J. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Cryst. 24, 946–950 (1991)

    Article  Google Scholar 

  46. Esnouf, R. M. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J. Mol. Graph. Model. 15, 132–134 (1997)

    Article  CAS  Google Scholar 

  47. Merritt, E. A. & Bacon, D. J. Raster3D: photorealistic molecular graphics. Methods Enzymol. 277, 505–524 (1997)

    Article  CAS  Google Scholar 

  48. Kudryashov, D. S. et al. The crystal structure of a cross-linked actin dimer suggests a detailed molecular interface in F-actin. Proc. Natl Acad. Sci. USA 102, 13105–13110 (2005)

    Article  ADS  CAS  Google Scholar 

  49. Allingham, J. S., Zampella, A., D’Auria, M. V. & Rayment, I. Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity. Proc. Natl Acad. Sci. USA 102, 14527–14532 (2005)

    Article  ADS  CAS  Google Scholar 

  50. Rizvi, S. A., Tereshko, V., Kossiakoff, A. A. & Kozmin, S. A. Structure of bistramide A-actin complex at a 1.35 angstroms resolution. J. Am. Chem. Soc. 128, 3882–3883 (2006)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank K. C. Holmes for continuous encouragement and D. Hanein for the gift of the atomic coordinates of the Volkmann et al. model (ref. 24). We thank K. Namba, K. Makino and K. Hasegwa for comments on the manuscript, the gift of software package for the fibre analysis and help with recording the diffraction patterns. We also thank S. Fujiwara and K. Mihashi for comments on the manuscript. We finally thank beam-line staffs at SPring-8 BL40B2, BL41XU and BL45XU-SAX, especially M. Kawamoto and K. Ito. The electron microscopy section of this study is partially supported by the Kazato Research Foundation (A.N.).

Author Contributions The X-ray fibre diffraction analysis for F-actin structure was performed by T.O. The mutant analysis of actin was conducted by M.I. and T.A. The structural analysis for the F-actin structure by the use of the electron cryomicroscopy analysis was conducted by A.N. Manuscript preparation was done by T.O. together with Y.M.

Author information

Authors and Affiliations

  1. X-ray Structural Analysis Research Team, RIKEN SPring-8 Center, RIKEN Harima Institute, 1-1-1, Kouto, Sayo, Hyogo 679-5148, Japan ,

    Toshiro Oda & Tomoki Aihara

  2. ERATO project ‘Actin-filament dynamics’, Japan Science and Technology Agency (JST), 1-1-1, Kouto, Sayo, Hyogo 679-5148, Japan ,

    Toshiro Oda, Mitsusada Iwasa & Yuichiro Maéda

  3. Structural Biology Research Center and Division of Biological Science, Graduate School of Science, Nagoya University, Furo, Nagoya 464-8601, Japan,

    Yuichiro Maéda & Akihiro Narita

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  1. Toshiro Oda
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Corresponding author

Correspondence to Toshiro Oda.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-9 with Legends, and Supplementary References, Supplementary Methods with Supplementary Methods Figures 1-5 with Legends and Supplementary Methods References. (PDF 2452 kb)

Atomic coordinates 1

This file contains the atomic coordinates 1-monomer.pdb (TXT 159 kb)

Atomic coordinates 2

This file contains the atomic coordinates 3- monomer.pdb (TXT 477 kb)

Supplementary Video 1

Supplementary Video 1 shows comparison of our F-actin model and the Holmes 2003 model with the EM map. (See nature07685-s1 for full movie legend). (MOV 4209 kb)

Supplementary Video 2

Supplementary Video 2 shows comparison of our F-actin model and the Volkmann model with the EM map.(See nature07685-s1 for full movie legend). (MOV 4406 kb)

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Oda, T., Iwasa, M., Aihara, T. et al. The nature of the globular- to fibrous-actin transition. Nature 457, 441–445 (2009). https://doi.org/10.1038/nature07685

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