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Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers.

<div class='caption-title'>(A) Schematic domain structure of a Drosophila Kinesin-5 subunit (KLP61F). The bipolar assembly (BASS domain) is denoted by rainbow colors. The motor domain, N-terminal coiled-coil domain, the C-terminal helical domain, and tail domain are shown in green, blue, red, and yellow respectively. (B) Schematic of the Kinesin-5 tetramer. (C) Upper panel: Gel filtration (also known as, size exclusion or molecular sieve) chromatography (GFC) of BASS and Selenium-substituted BASS (BASS-Se); lower panel, purification steps of BASS and SDS-PAGE of GFC fractions. Table 2 describes measured hydrodynamic properties of wt-BASS protein. (D) Negative stain electron microscopy (EM) of BASS tetramers. (E) Statistical analysis of BASS lengths measured using negative stain EM images describes an average length of 220 Å.</div>
<div class='caption-title'>Views of the BASS crystal unit cell displaying the packing of two BASS-dimer asymmetric units within the P6422 unit cell.</div>
<div class='caption-title'>(A) Side view of the crystal structure of the KLP61F BASS tetramer (residues 640–796 shown) colored in rainbow, starting with N-termini in blue traversing to C-termini in red, respectively. Four monomers pack as anti-parallel pairs of anti-parallel coiled-coil dimers. (B) shows the BASS structure rotated 90° around the filament axis relative to panel A. The dimensions of the BASS tetramer bundle structure are shown. (C) Side view of the BASS tetramer, with two BASS anti-parallel dimers colored in blue and red, respectively. (D) Detailed interaction between two monomers in the BASS anti-parallel dimer. (E) A 60° rotated view of D.</div>
Scholey JE, Nithianantham S, Scholey JM, Al-Bassam J
OpenAccess logo Elife 3 e02217 (2014)
Cited: 50 times
EuropePMC logo PMID: 24714498

Abstract

Chromosome segregation during mitosis depends upon Kinesin-5 motors, which display a conserved, bipolar homotetrameric organization consisting of two motor dimers at opposite ends of a central rod. Kinesin-5 motors crosslink adjacent microtubules to drive or constrain their sliding apart, but the structural basis of their organization is unknown. In this study, we report the atomic structure of the bipolar assembly (BASS) domain that directs four Kinesin-5 subunits to form a bipolar minifilament. BASS is a novel 26-nm four-helix bundle, consisting of two anti-parallel coiled-coils at its center, stabilized by alternating hydrophobic and ionic four-helical interfaces, which based on mutagenesis experiments, are critical for tetramerization. Strikingly, N-terminal BASS helices bend as they emerge from the central bundle, swapping partner helices, to form dimeric parallel coiled-coils at both ends, which are offset by 90°. We propose that BASS is a mechanically stable, plectonemically-coiled junction, transmitting forces between Kinesin-5 motor dimers during microtubule sliding. DOI: http://dx.doi.org/10.7554/eLife.02217.001.

Articles - 4pxt mentioned but not cited (2)

  1. Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers. Scholey JE, Nithianantham S, Scholey JM, Al-Bassam J. Elife 3 e02217 (2014)
  2. Using the Predicted Structure of the Amot Coiled Coil Homology Domain to Understand Lipid Binding. Peck C, Virtanen P, Johnson D, Kimble-Hill AC. Indiana Univ J Undergrad Res 4 27-46 (2018)


Reviews citing this publication (8)

  1. Coiled-coils: The long and short of it. Truebestein L, Leonard TA. Bioessays 38 903-916 (2016)
  2. The mechanics of microtubule networks in cell division. Forth S, Kapoor TM. J Cell Biol 216 1525-1531 (2017)
  3. Anaphase B. Scholey JM, Civelekoglu-Scholey G, Brust-Mascher I. Biology (Basel) 5 E51 (2016)
  4. Metaphase Spindle Assembly. Kapoor TM. Biology (Basel) 6 E8 (2017)
  5. Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles. Singh SK, Pandey H, Al-Bassam J, Gheber L. Cell Mol Life Sci 75 1757-1771 (2018)
  6. Centrosome instability: when good centrosomes go bad. Ryniawec JM, Rogers GC. Cell Mol Life Sci 78 6775-6795 (2021)
  7. Mechanisms by Which Kinesin-5 Motors Perform Their Multiple Intracellular Functions. Pandey H, Popov M, Goldstein-Levitin A, Gheber L. Int J Mol Sci 22 6420 (2021)
  8. Kinesin Motors in the Filamentous Basidiomycetes in Light of the Schizophyllum commune Genome. Raudaskoski M. J Fungi (Basel) 8 294 (2022)

Articles citing this publication (40)

  1. Measuring Pushing and Braking Forces Generated by Ensembles of Kinesin-5 Crosslinking Two Microtubules. Shimamoto Y, Forth S, Kapoor TM. Dev Cell 34 669-681 (2015)
  2. Determinants of Polar versus Nematic Organization in Networks of Dynamic Microtubules and Mitotic Motors. Roostalu J, Rickman J, Thomas C, Nédélec F, Surrey T. Cell 175 796-808.e14 (2018)
  3. Mechanical design principles of a mitotic spindle. Ward JJ, Roque H, Antony C, Nédélec F. Elife 3 e03398 (2014)
  4. Schizosaccharomyces pombe kinesin-5 switches direction using a steric blocking mechanism. Britto M, Goulet A, Rizvi S, von Loeffelholz O, Moores CA, Cross RA. Proc Natl Acad Sci U S A 113 E7483-E7489 (2016)
  5. Condensation of Ede1 promotes the initiation of endocytosis. Kozak M, Kaksonen M. Elife 11 e72865 (2022)
  6. A potential physiological role for bi-directional motility and motor clustering of mitotic kinesin-5 Cin8 in yeast mitosis. Shapira O, Goldstein A, Al-Bassam J, Gheber L. J Cell Sci 130 725-734 (2017)
  7. A novel chromosome segregation mechanism during female meiosis. McNally KP, Panzica MT, Kim T, Cortes DB, McNally FJ. Mol Biol Cell 27 2576-2589 (2016)
  8. KIF15 nanomechanics and kinesin inhibitors, with implications for cancer chemotherapeutics. Milic B, Chakraborty A, Han K, Bassik MC, Block SM. Proc Natl Acad Sci U S A 115 E4613-E4622 (2018)
  9. Motile properties of the bi-directional kinesin-5 Cin8 are affected by phosphorylation in its motor domain. Shapira O, Gheber L. Sci Rep 6 25597 (2016)
  10. The Kinesin-5 Chemomechanical Cycle Is Dominated by a Two-heads-bound State. Chen GY, Mickolajczyk KJ, Hancock WO. J Biol Chem 291 20283-20294 (2016)
  11. The kinesin-5 tail domain directly modulates the mechanochemical cycle of the motor domain for anti-parallel microtubule sliding. Bodrug T, Wilson-Kubalek EM, Nithianantham S, Thompson AF, Alfieri A, Gaska I, Major J, Debs G, Inagaki S, Gutierrez P, Gheber L, McKenney RJ, Sindelar CV, Milligan R, Stumpff J, Rosenfeld SS, Forth ST, Al-Bassam J. Elife 9 e51131 (2020)
  12. Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality. Düselder A, Fridman V, Thiede C, Wiesbaum A, Goldstein A, Klopfenstein DR, Zaitseva O, Janson ME, Gheber L, Schmidt CF. J Biol Chem 290 16841-16850 (2015)
  13. Src family kinase phosphorylation of the motor domain of the human kinesin-5, Eg5. Bickel KG, Mann BJ, Waitzman JS, Poor TA, Rice SE, Wadsworth P. Cytoskeleton (Hoboken) 74 317-330 (2017)
  14. Ensembles of Bidirectional Kinesin Cin8 Produce Additive Forces in Both Directions of Movement. Fallesen T, Roostalu J, Duellberg C, Pruessner G, Surrey T. Biophys J 113 2055-2067 (2017)
  15. Three Cdk1 sites in the kinesin-5 Cin8 catalytic domain coordinate motor localization and activity during anaphase. Goldstein A, Siegler N, Goldman D, Judah H, Valk E, Kõivomägi M, Loog M, Gheber L. Cell Mol Life Sci 74 3395-3412 (2017)
  16. Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast. Yukawa M, Okazaki M, Teratani Y, Furuta K, Toda T. Sci Rep 9 7336 (2019)
  17. Family-specific Kinesin Structures Reveal Neck-linker Length Based on Initiation of the Coiled-coil. Phillips RK, Peter LG, Gilbert SP, Rayment I. J Biol Chem 291 20372-20386 (2016)
  18. Mitotic kinesins: a reason to delve into kinesin-12. Hancock WO. Curr Biol 24 R968-70 (2014)
  19. Drag-induced directionality switching of kinesin-5 Cin8 revealed by cluster-motility analysis. Pandey H, Reithmann E, Goldstein-Levitin A, Al-Bassam J, Frey E, Gheber L. Sci Adv 7 eabc1687 (2021)
  20. A mechano-chemiosmotic model for the coupling of electron and proton transfer to ATP synthesis in energy-transforming membranes: a personal perspective. Kasumov EA, Kasumov RE, Kasumova IV. Photosynth Res 123 1-22 (2015)
  21. Mechanism for Anaphase B: Evaluation of "Slide-and-Cluster" versus "Slide-and-Flux-or-Elongate" Models. Brust-Mascher I, Civelekoglu-Scholey G, Scholey JM. Biophys J 108 2007-2018 (2015)
  22. The microtubule cross-linker Feo controls the midzone stability, motor composition, and elongation of the anaphase B spindle in Drosophila embryos. Wang H, Brust-Mascher I, Scholey JM. Mol Biol Cell 26 1452-1462 (2015)
  23. Acentrosomal spindle assembly and maintenance in Caenorhabditis elegans oocytes requires a kinesin-12 nonmotor microtubule interaction domain. Wolff ID, Hollis JA, Wignall SM. Mol Biol Cell 33 ar71 (2022)
  24. New tetrameric forms of the rotavirus NSP4 with antiparallel helices. Kumar S, Ramappa R, Pamidimukkala K, Rao CD, Suguna K. Arch Virol 163 1531-1547 (2018)
  25. Using a comprehensive approach to investigate the interaction between Kinesin-5/Eg5 and the microtubule. Guo W, Sun S, Sanchez JE, Lopez-Hernandez AE, Ale TA, Chen J, Afrin T, Qiu W, Xie Y, Li L. Comput Struct Biotechnol J 20 4305-4314 (2022)
  26. Mislocalization of TORC1 to Lysosomes Caused by KIF11 Inhibition Leads to Aberrant TORC1 Activity. Jang YG, Choi Y, Jun K, Chung J. Mol Cells 43 705-717 (2020)
  27. A surprising twist. Fakhri N, Schmidt CF. Elife 3 e02715 (2014)
  28. Distinct regions of the kinesin-5 C-terminal tail are essential for mitotic spindle midzone localization and sliding force. Gergely ZR, Jones MH, Zhou B, Cash C, McIntosh JR, Betterton MD. Proc Natl Acad Sci U S A 120 e2306480120 (2023)
  29. Flexible microtubule anchoring modulates the bi-directional motility of the kinesin-5 Cin8. Pandey H, Singh SK, Sadan M, Popov M, Singh M, Davidov G, Inagaki S, Al-Bassam J, Zarivach R, Rosenfeld SS, Gheber L. Cell Mol Life Sci 78 6051-6068 (2021)
  30. Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development. Yu WX, Li YK, Xu MF, Xu CJ, Chen J, Wei YL, She ZY. Cell Death Discov 8 490 (2022)
  31. Kinesin-5 Eg5 mediates centrosome separation to control spindle assembly in spermatocytes. She ZY, Zhong N, Wei YL. Chromosoma 131 87-105 (2022)
  32. The kinesin-5 protein Cut7 moves bidirectionally on fission yeast spindles with activity that increases in anaphase. Gergely ZR, Ansari S, Jones MH, Zhou B, Cash C, McIntosh R, Betterton MD. J Cell Sci 136 jcs260474 (2023)
  33. Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC. Indorato RL, DeBonis S, Garcia-Saez I, Skoufias DA. Front Oncol 12 965455 (2022)
  34. Effect of Kinesin-5 Tail Domain on Motor Dynamics for Antiparallel Microtubule Sliding. Liu Y, Wang Y, Wang P, Xie P. Int J Mol Sci 22 7857 (2021)
  35. Human kinesin-5 KIF11 drives the helical motion of anti-parallel and parallel microtubules around each other. Meißner L, Niese L, Schüring I, Mitra A, Diez S. EMBO J 43 1244-1256 (2024)
  36. Intracellular functions and motile properties of bi-directional kinesin-5 Cin8 are regulated by neck linker docking. Goldstein-Levitin A, Pandey H, Allhuzaeel K, Kass I, Gheber L. Elife 10 e71036 (2021)
  37. A stable microtubule bundle formed through an orchestrated multistep process controls quiescence exit. Laporte D, Massoni-Laporte A, Lefranc C, Dompierre J, Mauboules D, Nsamba ET, Royou A, Gal L, Schuldiner M, Gupta ML, Sagot I. Elife 12 RP89958 (2024)
  38. Kinesin-14 HSET and KlpA are non-processive microtubule motors with load-dependent power strokes. Liu X, Rao L, Qiu W, Berger F, Gennerich A. Nat Commun 15 6564 (2024)
  39. Noncanonical interaction with microtubules via the N-terminal nonmotor domain is critical for the functions of a bidirectional kinesin. Singh SK, Siegler N, Pandey H, Yanir N, Popov M, Goldstein-Levitin A, Sadan M, Debs G, Zarivach R, Frank GA, Kass I, Sindelar CV, Zalk R, Gheber L. Sci Adv 10 eadi1367 (2024)
  40. The kinesin-5 tail and bipolar minifilament domains are the origin of its microtubule crosslinking and sliding activity. Nithianantham S, Iwanski MK, Gaska I, Pandey H, Bodrug T, Inagaki S, Major J, Brouhard GJ, Gheber L, Rosenfeld SS, Forth S, Hendricks AG, Al-Bassam J. Mol Biol Cell 34 ar111 (2023)


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