Fig 3. Functional role of the bending motions in the coiled-coil region of fibrinogen.

(a) DisEMBL “hot coil” predictions for the sequences of the γ chain from several vertebrates, highlighting the fact that the flexibility of the non-helical loop is a conserved feature. The hinge region is shaded and, within that region, the non-helical loop segment is dark shaded. The inset legend reports the sequence alignment of the non-helical loop region across the same vertebrates, highlighting the content of glycine and proline residues. (b) Cartoon representation of the coiled-coil region of Fg colored according to the fraction of the simulation time spent in an α-helical conformation (red = 0, green = 0.85, blue = 1). The N-termini of the segments are on the left. The regions with lower helical fraction are in good agreement with regions with lower protection factors as determined in H/D exchange experiments [29]. (c) Probability distribution of the fraction of helical residues around the Aα104–105 and Bβ133–134 plasmin cleavage sites as a function of the bending angle γ. Dark shades correspond to high probability. The three residues preceding and following the cleavage sites (i.e., Aα102–107 and Bβ131–136) have been included in the calculation of the helicity. Larger bending (lower γ angle) correlates with lower helical content. (d) Snapshot of the conformation of the bent coiled-coil region (chains colored as in Fig 1) showing the disrupted secondary structure around the plasmin cleavage sites (rendered yellow and cyan inside the dashed circle).