Fig 1.
Structural models of the keratin dimer.
(A) Schematic of the domain structure of the keratin dimer. (B) The number of residues in each subdomain. (C) Initial starting arrangements for the head domain, shown projected out of the 1A domain (values refer to the number of truncated/full dimer models considered). (D) An example of equilibrated dimer structure annotated with the mean principal component dimensions for each major domain and the hinge angle across the L1 and L12 linker.
Fig 2.
Positioning of the head domain.
(A) Three exemplar positional preferences of the head domain. (B and E) Schematics of 1A and head domain showing key measurements made on V1 and E1 head domains (definitions of vectors are given in Methods). (C and F) plots of the occurrence of the positions taken by the V1 globule and N-term of the E1 head domain, respectively, with annotations referring to the examples. (D) top down diagrams illustrating the radial positioning of the head domain and the heptad positions of the 1A rod domain (the N-termini of the 1A starts at the e-heptad position and then runs clockwise into the page).
Fig 3.
Positioning of the tail domain.
(A) Exemplar positional preferences of the tail domain. (B and E) schematics of 2B and tail domain showing key measurements made on V2 and E2 head domains (definitions of vectors are given in Methods). (C and F) plots of the occurrence of the positions taken by the V2 globules and C-term of the E2 tail domain, respectively. (D) bottom down diagrams showing the radial positioning of the tail domain and the heptad positions of the 2B rod domain.
Fig 4.
(A) Example final dimer structures with secondary structure shown on the left and residue type shown on the right. (B) Local radius and pitch of the coiled-coil subdomains 1A (left), 1B (center) and 2A-L2-2B (right) obtained from simulations using implicit solvent. (C) The same plot showing a comparison of four dimer models obtained using implicit solvent or explicit solvent and experimental crystal structure data of vimentin and keratin K5/K14. (D) comparison of the side chain contacts of the 2A-L2-2B rod domain, between our models of keratin K1/K10 in explicit water and the K5/K14 crystal structure. For clarity only contacts with at least a 0.5 probability of occurrence in the models are shown.
Fig 5.
(A) Combined contact plots for the head domain and part of the rod domain showing the probability of the Cα atoms of a pair of residues being separated by less than 12 Å. The dashed-lines show the boundaries between the head domain and rod subdomains, and dotted-lines indicate changes in the characteristics of the primary sequence (see Section E in S1 File). The letter annotations show which residues correspond to the rod subdomains 1A, L1 and 1B and our proposed head subdomains (H1, V1, E1). The red box indicates the residues that make up glycine loop motifs. (B) Snapshot of the head domain showing the aromatic and glycine loops contained within. (C) Snapshot of the head domain highlighting the acidic (red) and basic residues (blue) interacting between the rod and head domains. The rectangle indicates the location of acid and base pairing between the 1A rod domain and H1 head domain.
Fig 6.
(A) Combined contact plots for part of the rod domain and tail domain showing for the probability of the Cα atoms of a pair of residues being separated by less than 12 Å. The dashed-lines show the standard boundaries between the rod domain and tail subdomains, and dotted-lines indicate changes in the characteristics of the primary sequence (see Section E in S1 File). The letter annotations show which residues correspond to the rod subdomains 2B and our proposed head subdomains (H2, V2, E2). (B) Snapshot of the tail domain showing the aromatic (in green) and glycine loops (yellow ribbon) contained within. (C) Snapshot highlighting the acid (red) and basic residues (blue) interacting between the rod and tail domains (inside box).
Fig 7.
(A and B) Models of the head (A) and tail (B) domains with annotations indicating the local electrostatic polarity. (C) Proposed form for the A11 tetramer. (D) Proposed stutter-twisted form for the protofilament.