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
• 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 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:
The Condensin Family
Prokaryotic Condensin
Structured Maintainance of
Chromosomes (SMC) proteins
Eukaryotic Condensin
ATP binding at SMC heads
Proteins containing HEAT
repeats
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 and II axis definition
•Condensin I defines long axis of Chromosome
•Condensin II defines perpendicular axis/plane through both Chromosome
arms
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)
Condensin 1
• Axis extends to span multiple chromosomes
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)
Condensin II
• creates a plane that sets the location of centrosomes
centrosomes
HEAT repeat structure – Importin beta
HEAT repeat structure
• The original ‘cork and bead’ model
HEAT repeat structure – A more compact form?
• Rings of 5 inner (yellow) helixes around an elongated core
• One helix (green) spans two rings
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
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
Structured Maintainance of
Chromosomes (SMC) proteins
Eukaryotic Condensin
ATP binding at SMC heads
Proteins containing HEAT
repeats
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
Structured Maintainance of
Chromosomes (SMC) proteins
Eukaryotic Condensin
ATP binding at SMC heads
Proteins containing HEAT
repeats
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.