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Resonant vibrations in HEAT repeats:  the tune for the mitotic dance?

Resonant vibrations in HEAT repeats:  the tune for the mitotic dance?. Nigel Dyer UK. Professor Herbert Frohlich. A single polarised macromolecule, e.g. a protein. Preferential excitement of large amplitude low frequency modes. Multiple polarised proteins.

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Resonant vibrations in HEAT repeats:  the tune for the mitotic dance?

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  1. Resonant vibrations in HEAT repeats:  the tune for the mitotic dance? Nigel Dyer UK

  2. Professor Herbert Frohlich

  3. A single polarised macromolecule, e.g. a protein Preferential excitement of large amplitude low frequency modes

  4. Multiple polarised proteins Coherent vibrational mode through dipole-dipole interaction

  5. HEAT repeat structure – Importin beta A ladder of helix-turn-helix motifs Outer ‘A’ helixes and inner ‘B’ helixes surround a central importin beta alpha helix (blue)

  6. Proteins containing HEAT repeats • Condensin: Compacts Chromosomes • Importin: Transports cargo into the cell nucleus • TOGp (XMAP215 etc): Associated with the ends of microtubules as they grow towards the chromosomes during mitosis. Others… • Delangins: Locates the cohesin complex within chromosomes • Huntington:

  7. The Condensin Family Prokaryotic Condensin Structured Maintainance of Chromosomes (SMC) proteins Eukaryotic Condensin ATP binding at SMC heads Proteins containing HEAT repeats

  8. Effect of disabling Condensin I and II (Ono, Losada et al. 2003) e: Control f: Condensin I disabled: Puffy and bent g: Condensin II disabled: Straighter but curly

  9. Group of coherently vibrating proteins with misalignment

  10. Interaction brings proteins into alignment

  11. Mitotic chromosome: Condensins disabled Condensin I (Green) aligned along chromosome axis

  12. Condensin I Aligning of Condensin I straightens Chromosome arms

  13. Condensin II Condensin II (Blue) orthogonal to main axis Not aligned with each other because main axis is twisted

  14. Condensin II Aligning force from condensin II removes twist from chromosome arms

  15. Condensin I and II Both act to draw together and align chromosome arms

  16. Condensin I and II axis definition Condensin I defines long axis of Chromosome Condensin II defines perpendicular axis/plane through both Chromosome arms

  17. Effect of depleted Condensin I on metaphase plate • Control, with well defined metaphase plate • Depleted Condensin 1 Poorly defined metaphase plates (From Ono, Fang et al. 2004)

  18. Condensin 1 Axis extends to span multiple chromosomes

  19. Effect of depleted Condensin II on metaphase plate • Control, with centrosomes (arrowed) symmetrically placed on either side of the metaphase plate (dotted line) • Depleted Condensin II • Centrosomes poorly positioned in relation to metaphase plate (From Ono, Fang et al. 2004)

  20. centrosomes Condensin II creates a plane that sets the location of centrosomes

  21. HEAT repeat structure – Importin beta

  22. HEAT repeat structure The original ‘cork and bead’ model

  23. HEAT repeat structure – A more compact form? Rings of 5 inner (yellow) helixes around an elongated core One helix (green) spans two rings

  24. HEAT repeat structure View along the length of Importin alpha/beta complex End on view of Importin alpha/beta complex, with no side chains on the IBB domain of importin alpha

  25. HEAT repeat vibrating in cellular matrix Inner core and outer sheath oscillate 180° out of phase No movement of centre of mass Vibrations spread as evanescent wave into the surrounding substrate

  26. HEAT repeat resonant energy transfer Energy coupled from excited structure (on right) to adjacent structure (on left) Both structures finish in coherent synchronous oscillation

  27. HEAT repeat alignment HEAT repeats oscillating but slightly misaligned Non-linear interaction of evanescent waves generates forces that bring HEAT repeats into alignment.

  28. The Condensin Family Prokaryotic Condensin Structured Maintainance of Chromosomes (SMC) proteins Eukaryotic Condensin ATP binding at SMC heads Proteins containing HEAT repeats

  29. SMC proteins/Prokaryotic Condensin Thermally induced breathing modes in long coiled coil legs Pulls DNA together during contraction phase of oscillation

  30. Walker A/B domain and binding ATP SMC head binding with ATP ATP binds heads together in Prokaryotic condensin at Walker A/B domains Walker A/B domains in ABC transporter proteins associated with mysoin like power stroke

  31. The Condensin Family Prokaryotic Condensin Structured Maintainance of Chromosomes (SMC) proteins Eukaryotic Condensin ATP binding at SMC heads Proteins containing HEAT repeats

  32. HEAT repeats in TOGp/XMAP 215 TOGp is associated with the growing ends of the microtubules as they extend towards the chromosomes in the metaphase plate TOGp (red)

  33. HEAT repeats in Importin beta Importin beta attaches to cargos and transfers them into the nucleus Importin beta (green) Cell nucleus

  34. The Nuclear pore complex Core of complex filled with nucleoporin proteins, a mix of multiple FG repeats and hydrophilic linkers Pore blocked by water gell created by nucleoporin proteins?

  35. Passage of Importin through the Nuclear pore complex Gel/water transition triggered by Importin vibrations

  36. Central formers for HEAT repeats • Importin beta: Importin alpha • Condensin: Histone H3 tails (Jager, Rauch et al. 2005) • TOGp/XMAP215 Tubulin tails

  37. centrosomes Orthogonal condensin axes and orthogonal centrioles Centriole pair

  38. Thanks to: • Vermont Photonics • Warwick University • Lila Gierasch, Gerry Pollack, Mae-wan Ho and countless others who I have visited and emailed • The creaters of Blender

  39. Biophoton emission from dividing fish egg cells ‘Cascades’ of biophoton spikes.

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