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Structural insight into filament formation by mammalian septins


Septins are GTP-binding proteins that assemble into homo- and hetero-oligomers and filaments. Although they have key roles in various cellular processes, little is known concerning the structure of septin subunits or the organization and polarity of septin complexes. Here we present the structures of the human SEPT2 G domain and the heterotrimeric human SEPT2–SEPT6–SEPT7 complex. The structures reveal a universal bipolar polymer building block, composed of an extended G domain, which forms oligomers and filaments by conserved interactions between adjacent nucleotide-binding sites and/or the amino- and carboxy-terminal extensions. Unexpectedly, X-ray crystallography and electron microscopy showed that the predicted coiled coils are not involved in or required for complex and/or filament formation. The asymmetrical heterotrimers associate head-to-head to form a hexameric unit that is nonpolarized along the filament axis but is rotationally asymmetrical. The architecture of septin filaments differs fundamentally from that of other cytoskeletal structures.

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Figure 1: Structure and dimerization of SEPT2.
Figure 2: Structural analysis of the human septin complex.
Figure 3: Electron microscopic studies of septin complexes.
Figure 4: The septin filament.


  1. 1

    Versele, M. & Thorner, J. Some assembly required: yeast septins provide the instruction manual. Trends Cell Biol. 15, 414–424 (2005)

    CAS  Article  Google Scholar 

  2. 2

    Kinoshita, M. The septins. Genome Biol. 4, 236 (2003)

    MathSciNet  Article  Google Scholar 

  3. 3

    Byers, B. & Goetsch, L. A highly ordered ring of membrane-associated filaments in budding yeast. J. Cell Biol. 69, 717–721 (1976)

    CAS  Article  Google Scholar 

  4. 4

    Haarer, B. K. & Pringle, J. R. Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10-nm filaments in the mother-bud neck. Mol. Cell. Biol. 7, 3678–3687 (1987)

    CAS  Article  Google Scholar 

  5. 5

    DeMarini, D. J. et al. A septin-based hierarchy of proteins required for localized deposition of chitin in the Saccharomyces cerevisiae cell wall. J. Cell Biol. 139, 75–93 (1997)

    CAS  Article  Google Scholar 

  6. 6

    Kozubowski, L. et al. A Bni4-Glc7 phosphatase complex that recruits chitin synthase to the site of bud emergence. Mol. Biol. Cell 14, 26–39 (2003)

    CAS  Article  Google Scholar 

  7. 7

    Kinoshita, M. Assembly of mammalian septins. J. Biochem. 134, 491–496 (2003)

    CAS  Article  Google Scholar 

  8. 8

    Macara, I. G. et al. Mammalian septins nomenclature. Mol. Biol. Cell 13, 4111–4113 (2002)

    CAS  Article  Google Scholar 

  9. 9

    Hall, P. A., Jung, K., Hillan, K. J. & Russell, S. E. H. Expression profiling the human septin gene family. J. Pathol. 206, 269–278 (2005)

    CAS  Article  Google Scholar 

  10. 10

    Kartmann, B. & Roth, D. Novel roles for mammalian septins: from vesicle trafficking to oncogenesis. J. Cell Sci. 114, 839–844 (2001)

    CAS  PubMed  Google Scholar 

  11. 11

    Hall, P. A. & Russell, S. E. H. The pathobiology of the septin gene family. J. Pathol. 204, 489–505 (2004)

    CAS  Article  Google Scholar 

  12. 12

    Kuhlenbaumer, G. et al. Mutations in SEPT9 cause hereditary neuralgic amyotrophy. Nature Genet. 37, 1044–1046 (2005)

    Article  Google Scholar 

  13. 13

    Mitchison, T. J. & Field, C. M. Cytoskeleton: What does GTP do for septins? Curr. Biol. 12, R788–R790 (2002)

    CAS  Article  Google Scholar 

  14. 14

    Kinoshita, M., Field, C. M., Coughlin, M. L., Straight, A. F. & Mitchison, T. J. Self- and actin-templated assembly of mammalian septins. Dev. Cell 3, 791–802 (2002)

    CAS  Article  Google Scholar 

  15. 15

    Hsu, S. C. et al. Subunit composition, protein interactions, and structures of the mammalian brain sec6/8 complex and septin filaments. Neuron 20, 1111–1122 (1998)

    CAS  Article  Google Scholar 

  16. 16

    Surka, M. C., Tsang, C. W. & Trimble, W. S. The mammalian septin MSF localizes with microtubules and is required for completion of cytokinesis. Mol. Biol. Cell 13, 3532–3545 (2002)

    CAS  Article  Google Scholar 

  17. 17

    Joberty, G. et al. Borg proteins control septin organization and are negatively regulated by Cdc42. Nature Cell Biol. 3, 861–866 (2001)

    CAS  Article  Google Scholar 

  18. 18

    Frazier, J. A. et al. Polymerization of purified yeast septins — evidence that organized filament arrays may not be required for septin function. J. Cell Biol. 143, 737–749 (1998)

    CAS  Article  Google Scholar 

  19. 19

    Oegema, K., Desai, A., Won, M. L., Mitchison, T. J. & Field, C. M. Purification and assay of a septin complex from Drosophila embryos. Methods Enzymol. 298, 279–295 (1998)

    CAS  Article  Google Scholar 

  20. 20

    Field, C. M. et al. A purified Drosophila septin complex forms filaments and exhibits GTPase activity. J. Cell Biol. 133, 605–616 (1996)

    CAS  Article  Google Scholar 

  21. 21

    Vrabioiu, A. M., Gerber, S. A., Gygi, S. P., Field, C. M. & Mitchison, T. J. The majority of the Saccharomyces cerevisiae septin complexes do not exchange guanine nucleotides. J. Biol. Chem. 279, 3111–3118 (2004)

    CAS  Article  Google Scholar 

  22. 22

    Farkasovsky, M., Herter, P., Voss, B. & Wittinghofer, A. Nucleotide binding and filament assembly of recombinant yeast septin complexes. Biol. Chem. 386, 643–656 (2005)

    CAS  Article  Google Scholar 

  23. 23

    Sheffield, P. J. et al. Borg/septin interactions and the assembly of mammalian septin heterodimers, trimers, and filaments. J. Biol. Chem. 278, 3483–3488 (2003)

    CAS  Article  Google Scholar 

  24. 24

    Nguyen, T. Q., Sawa, H., Okano, H. & White, J. G. The C. elegans septin genes, unc-59 and unc-61, are required for normal postembryonic cytokineses and morphogenesis but have no essential function in embryogenesis. J. Cell Sci. 113, 3825–3837 (2000)

    CAS  PubMed  Google Scholar 

  25. 25

    Mendoza, M., Hyman, A. A. & Glotzer, M. GTP binding induces filament assembly of a recombinant septin. Curr. Biol. 12, 1858–1863 (2002)

    CAS  Article  Google Scholar 

  26. 26

    Huang, Y. W., Surka, M. C., Reynaud, D., Pace-Asciak, C. & Trimble, W. S. GTP binding and hydrolysis kinetics of human septin 2. FEBS J. 273, 3248–3260 (2006)

    CAS  Article  Google Scholar 

  27. 27

    Leipe, D. D., Wolf, Y. I., Koonin, E. V. & Aravind, L. Classification and evolution of P-loop GTPases and related ATPases. J. Mol. Biol. 317, 41–72 (2002)

    CAS  Article  Google Scholar 

  28. 28

    Scrima, A. & Wittinghofer, A. Dimerisation-dependent GTPase reaction of MnmE: how potassium acts as GTPase-activating element. EMBO J. 25, 2940–2951 (2006)

    CAS  Article  Google Scholar 

  29. 29

    Gasper, R., Scrima, A. & Wittinghofer, A. Structural insights into HypB, a GTP-binding protein that regulates metal binding. J. Biol. Chem. 281, 27492–27502 (2006)

    CAS  Article  Google Scholar 

  30. 30

    Low, C. & Macara, I. G. Structural analysis of septin 2, 6, and 7 complexes. J. Biol. Chem. 281, 30697–30706 (2006)

    CAS  Article  Google Scholar 

  31. 31

    Boehringer, D. et al. Three-dimensional structure of a pre-catalytic human spliceosomal complex B. Nature Struct. Mol. Biol. 11, 463–468 (2004)

    CAS  Article  Google Scholar 

  32. 32

    van Heel, M. & Frank, J. Use of multivariate statistics in analysing the images of biological macromolecules. Ultramicroscopy 6, 187–194 (1981)

    CAS  PubMed  Google Scholar 

  33. 33

    Chant, J. Septin scaffolds and cleavage planes in Saccharomyces. Cell 84, 187–190 (1996)

    CAS  Article  Google Scholar 

  34. 34

    Vrabioiu, A. M. & Mitchison, T. J. Structural insights into yeast septin organization from polarized fluorescence microscopy. Nature 443, 466–469 (2006)

    CAS  Article  ADS  Google Scholar 

  35. 35

    Kabsch, W. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J. Appl. Cryst. 26, 795–800 (1993)

    CAS  Article  Google Scholar 

  36. 36

    Schneider, T. R. & Sheldrick, G. M. Substructure solution with SHELXD.. Acta Crystallogr D 58, 1772–1779 (2002)

    Article  Google Scholar 

  37. 37

    Terwilliger, T. C. SOLVE and RESOLVE: automated structure solution and density modification. Methods Enzymol. 374, 22–37 (2003)

    CAS  Article  Google Scholar 

  38. 38

    CCP4. The CCP4 (Collaborative Computational Project Number 4) suite: programs for protein crystallography. Acta Crystallogr. D 50, 760–763 (1994)

  39. 39

    Emsley, P. &. Cowtan, K. Coot: Model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126–2132 (2004)

    Article  Google Scholar 

  40. 40

    Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240–255 (1997)

    CAS  Article  Google Scholar 

  41. 41

    Brunger, A. T. et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D 54, 905–921 (1998)

    CAS  Article  Google Scholar 

  42. 42

    DeLano, W. L. The PyMOL Molecular Graphics System 〉 (2006)

    Google Scholar 

  43. 43

    Dube, P., Tavares, P., Lurz, R. & van Heel, M. The portal protein of bacteriophage SPP1: a DNA pump with 13-fold symmetry. EMBO J. 12, 1303–1309 (1993)

    CAS  Article  Google Scholar 

  44. 44

    van Heel, M. & Frank, J. Use of multivariate statistics in analysing the images of biological macromolecules. Ultramicroscopy 6, 187–194 (1981)

    CAS  PubMed  Google Scholar 

  45. 45

    van Heel, M. Classification of very large electron microscopical image data sets. Opik 82, 114–126 (1989)

    Google Scholar 

  46. 46

    Sander, B., Golas, M. M. & Stark, H. Corrim-based alignment for improved speed in single-particle image processing. J. Struct. Biol. 143, 219–228 (2003)

    CAS  Article  Google Scholar 

  47. 47

    van Heel, M., Harauz, G., Orlova, E. V., Schmidt, R. & Schatz, M. A new generation of the IMAGIC image processing system. J. Struct. Biol. 116, 17–24 (1996)

    CAS  Article  Google Scholar 

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Data collection was done at the Swiss Light Source, beam line X10SA, Paul Scherrer Institute, Villigen, Switzerland, and we thank the beam line staff for assistance. We would like to thank I. Vetter, I. Schlichting, T. Meinhart, W. Blankenfeldt, N. Schrader, E. Hofmann, K. Kühnel, A. Scrima, R. Gasper and R. Rose for data collection and crystallographic advice. M.S. and F.H. thank the International Max Planck Research School for financial support. This work was supported by the 3D Repertoire project, within the EU Sixth Framework Program, and the Fondation Louis-Jeantet.

Author Contributions M.S. purified and crystallized SEPT2-315 and the human septin complex and solved the structures. M.F. made the human septin complex constructs, developed the purification procedure and purified the yeast septin complex used in the electron microscopy. F.H. and H.S. did the electron microscopy analysis. D.K. made SEPT2-315 mutants. M.W. assisted M.S. throughout data collection and structure determination. I.G.M. provided the clones for human septins, and valuable hints. A.W. supervised the project and wrote the paper. All authors discussed the results and commented on the manuscript.

The atomic coordinates of SEPT2-315 and the human septin complex are deposited in the Protein Data Bank with accession numbers 2QA5 and 2QAG, respectively.

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Correspondence to Alfred Wittinghofer.

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Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Tables 1-4 describing the data collection, phasing, and refinement statistics and EM particle statistics, Supplementary Figures 1-3 with Legends showing sequence alignment of Sept2, 6 and 7 with secondary structural elements; details of Sept2 interface and raw electron density pictures of HSC. (PDF 569 kb)

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Sirajuddin, M., Farkasovsky, M., Hauer, F. et al. Structural insight into filament formation by mammalian septins. Nature 449, 311–315 (2007).

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