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. 2016 Feb 23;110(4):896–911. doi: 10.1016/j.bpj.2015.12.033

Figure 9.

Figure 9

The active conformations and receptor activation. (A) CBVS scores for zinc coordination by mutants modeled into the tight tetramer (gray bars), and the same analysis for tetramers in which the active dimers were allowed to relax as rigid bodies (orange bars). (B) Left panel: alignment of the tight tetramer (gray) and the translated-dimer structure optimized for coordination of zinc (orange sphere) by the HH mutant by rigid body translation of the dimers (orange). Right panel: coordination of zinc by the T4 mutant before and after rigid body translation. Modeling reveals steric clashes between T672H and K765H. (C) Sites of Arg660 (marker for subunits A/C, green spheres), Gln756 (marker for subunits B/D, blue spheres) and Pro632 (LBD-TM3 marker, red spheres) in the full-length receptor (gray, PDB: 4U2P). (D) Lateral positions of Pro632, aligned in plain view, are shown for apo conformation (red), CA in which the subunits B and D are modeled bound by glutamate (orange), and the tight tetramer (cyan). Arrows indicate the direction of Pro632 displacement from apo LBDs toward LBDs partially (CA) and fully (tight) populated by glutamate. (E) Displacements of Pro632, measured diagonally between the subunits (A-C) and (B-D) in the full-length receptor for apo (red), the glutamate bound active state model from EM (Glu_EM, blue), the partly bound conformation (CA, orange), the tight tetramer conformation before (tight, cyan) and after (HH-modeled, green) rigid body movement to accommodate zinc in the HH mutant. (F) Diagonally opposed residues at the core of the LBD tetramer Arg660 and Gln756, with the same color code as in (D). (G) Cartoon of proposed LBD movements during receptor activation, with the amino terminal domain omitted for clarity. The open angle, fully bound form represents the glutamate bound active state model from EM (Glu_EM). The open angle, partly bound form has not been captured in crystal structures, but is included here for completeness (indicated with a question mark). Cartoons are accompanied by ribbon representations of the respective LBDs (PDB IDs in brackets). Subunits are color coded as in Fig. 1A. Black arrows indicate vectors defined for determination of the interdimer angle between dimer pairs A-D and B-C with the vertex at the center of mass of 665 Cα atoms in subunits A and C (15). To see this figure in color, go online.