FIGURE 1.
α1/α7 helix T-junction formation and headpiece hinge opening are allosterically linked. A, FnIII10 (15) (yellow) docked to the integrin structure (13). Integrin α- and β-subunits are blue and gray, respectively. Domains not resolved in the crystal structure were added in pink. B, the headpiece complex was simulated with explicit water molecules. C, the region of the α1/α7 helix junction in the integrin headpiece is shown in the box. D, the βA and hybrid domains from the liganded αvβ3 integrin crystal structure (13), in black, are aligned with the same domains from the unliganded αvβ3 integrin crystal structure (11), shown in color (red for the β6-α7 loop and α7 helix, green for the β1-α1 loop and α1 helix, and transparent purple for everything else). E, the βA and hybrid domains from the liganded αvβ3 integrin crystal structure (13), in black, are aligned here with the same domains from the liganded αIIbβ3 integrin structure (12), shown in color. Where the hinge is closed in both structures (D), the greatest structural change is in the binding pocket. Where the difference in the hinge angle is ∼62° (E), the region of greatest change is that of the α1/α7 T-junction. F–H, the three integrin crystal structures are shown separately. MD-derived snapshots (I and J) are depicted beneath the starting structures to which they correspond (F and G, respectively). The β1-α1 loop/α1 helix and α7 helix/hybrid domain regions are shown in green and red, respectively. Residues of the β6-α7 loop and α7 helix shown space-filling in red are Leu343 and Ile344, located at the top of the α7 helix, Val247, Ile307, and Ala309, located on underlying β-strands, and Leu333, located where the β6-strand becomes the β6-α7 loop. Shown in space-filling in green are Leu134 and Leu138 in the α1 helix. Black arrows identify the region where the β1-α1 loop meets the α1 helix, and the region where the α1 helix comes in contact with the β6 strand and α7 helix during T-junction formation.