Resonant vibrations in HEAT repeats: 

the tune for the mitotic dance?

Nigel DyerUK

Professor Herbert Frohlich

A single polarised macromolecule, e.g. a protein

• Preferential excitement of large amplitude low frequency modes

Multiple polarised proteins

• Coherent vibrational mode through dipole-dipole interaction

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)

Proteins containing HEAT repeats

Condensin: Compacts Chromosomes Importin: Transports cargo into the cell nucleusTOGp (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:

The Condensin Family

Prokaryotic Condensin

ATP binding at SMC heads

Eukaryotic Condensin

Proteins containing HEAT repeats

Structured Maintainance of Chromosomes (SMC) proteins

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

Group of coherently vibrating proteins with misalignment

Interaction brings proteins into alignment

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

Condensin I

• Aligning of Condensin I straightens Chromosome arms

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

Condensin II

• Aligning force from condensin II removes twist from chromosome arms

Condensin I and II

• Both act to draw together and align chromosome arms

•Condensin I defines long axis of Chromosome•Condensin II defines perpendicular axis/plane through both Chromosome arms

Condensin I and II axis definition

Effect of depleted Condensin I on metaphase plate

(From Ono, Fang et al. 2004)

• Control, with well defined metaphase plate

• Depleted Condensin 1

Poorly defined metaphase plates

Condensin 1

• Axis extends to span multiple chromosomes

Effect of depleted Condensin II on metaphase plate

(From Ono, Fang et al. 2004)

•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

Condensin II

centrosomes

• creates a plane that sets the location of centrosomes

HEAT repeat structure – Importin beta

HEAT repeat structure

• The original ‘cork and bead’ model

• Rings of 5 inner (yellow) helixes around an elongated core• One helix (green) spans two rings

HEAT repeat structure – A more compact form?

End on view of Importin alpha/beta complex, with no side

chains on the IBB domain of importin alpha

View along the length of Importin alpha/beta complex

HEAT repeat structure

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

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

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

The Condensin Family

Prokaryotic Condensin

ATP binding at SMC heads

Eukaryotic Condensin

Proteins containing HEAT repeats

Structured Maintainance of Chromosomes (SMC) proteins

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

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

Walker A/B domain and binding ATP

The Condensin Family

Prokaryotic Condensin

ATP binding at SMC heads

Eukaryotic Condensin

Proteins containing HEAT repeats

Structured Maintainance of Chromosomes (SMC) proteins

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)

HEAT repeats in Importin beta• Importin beta attaches to cargos and transfers them into the nucleus

Importin beta (green) Cell nucleus

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?

Passage of Importin through the Nuclear pore complex

• Gel/water transition triggered by Importin vibrations

Central formers for HEAT repeats

• Importin beta: Importin alpha

• Condensin: Histone H3 tails (Jager, Rauch et al. 2005)

• TOGp/XMAP215 Tubulin tails

Orthogonal condensin axes and orthogonal centrioles

centrosomes

Centriole pair

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

Biophoton emission from dividing fish egg cells

• ‘Cascades’ of biophoton spikes.