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