FIGURE LEGENDS
Figure 1
The “knobs in holes” coiled-coil interface of Crick .
Parallel α-helices are represented as flattened sheets, with the red
helix on the bottom (with side chains pointing towards the viewer) and
the blue helix on the top (with side chains pointing away from the
viewer). If the top helix is rotated 20° counterclockwise its side
chains (“knobs”) juxtapose with the spaces (“holes”) between side
chains in the bottom helix. This rotation leads to left-handed
supercoiling that alters the helical twist from 3.6 to 3.5 residues per
turn, resulting in a heptad repeat (right). Hydrophobic side chain
patterning conforming to a heptad repeat thereby promotes the
coiled-coil interaction 1,2
Figure 2
Hypothesized leucine “Zipper”, “jigsaw”, and “Velcro”
coiled-coil interface . The interdigitation of the γ-branched leucine
side chain (panel A) was postulated to “lock” coiled-coil α-helices
together in a form of steric entanglement (i.e., the “leucine zipper”)
(panel B) (after Landschultz, 1988) 7. Panels C-D
illustrate the steric entanglement of physical interfaces of a zipper,
jigsaw pieces and Velcro™ (hook and loop interface), respectively. Each
of these objects have been invoked to describe the coiled coil
interface.
Figure 3
The Monofoil homotrimer and circular permutants . The Symfoil
protein is a de novo designed symmetric β-trefoil protein having three
exact repeats of a 42-mer “trefoil” motif 22,23.
Expression of the isolated trefoil motif (“Monofoil”) yields a stably
folded trimeric oligomer regenerating an intact β-trefoil fold. Circular
permutation at each turn position in the trefoil motif yields three
different permutants (#1-3).
Figure 4
3D printed model of the Monofoil permutant P2 trimer oligomeric
assembly . The 40-mer Monofoil permutant P2 polypeptide was 3D printed
in white, black and orange TPU. The individual peptide models were
assembled to form an intact β-trefoil architecture. The view is down the
threefold axis of rotational symmetry. This structure exhibits extreme
entanglement (Fig. 5).
Figure 5
Kinetic energy of dissociation for 3D printed protein
oligomers . Upper panel: Dissociation of coiled-coils of 28-mer
polyleucine in either all trans or all gauche+ rotamers,
and either parallel or anti-parallel orientations. Lower panel:
Dissociation of trimeric assemblies of the Monofoil trefoil motif
(forming a β-trefoil) and with different circular permutations of the
domain-swapped interface (see Fig. 3).
Figure 6
Protein interface entanglement and kinetic trapping .
Entanglement of a protein oligomerization interface can result in an
increased energy barrier to unfolding (red). This barrier can lead to
kinetic trapping of the unfolding pathway. The reaction coordinate
diagram also illustrates how a high energy intermediate will also lead
to similar kinetic trapping of the folding pathway.
Figure 1