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. 2015 Aug 6;109(6):1136–1148. doi: 10.1016/j.bpj.2015.06.061

Figure 4.

Figure 4

(A and B) Monomer and dimer conformational changes are coupled to motions of NTD tetramers and whole receptors in both NMDARs (A) and AMPARs (B). Matrices comparing the modes of motion of these smaller systems with progressively larger systems are represented as colored squares. Darker colors indicate higher correlations. Red (positive correlations) and blue (negative correlations) are equivalent, as ANM modes are harmonic fluctuations with arbitrary starting directions. The bottom matrix (panel 1) shows the overlap between modes of monomer motions (ordinate, label on far right and shared by AMPARs and NMDARs) and dimer motions (abscissa). A zoom into the first few elements illustrates that many dimer modes show a significant overlap with both prominent modes of monomer motion. The matrix above (panel 2) compares the same dimer modes of motion (shared abscissa) with the modes of motion of the NTD tetramer (ordinate, label on far right). In this case, there are many darker blocks, indicating a higher correlation. The top-left matrix shows the overlap between the motions of the NTD tetramer and those of the whole receptor. The starting structure for the AMPAR is a GluA2 homotetramer (18); the NMDAR is a GluN1/2B heteromer (PDB ID: 4PE5) (16). Lines connect some modes of motion that show good correlations all the way from monomers to whole receptors. Dimeric motions are more conserved through the levels in the NMDAR, as illustrated for dimer mode 1, where dark dots illustrate good correlations along the way and the endpoints are the circled modes 6–8 of the whole NMDAR. The monomer shown is GluN1, where cleft motions are also well retained. In the AMPAR monomer, cleft motions are again retained but dimer rearrangements are dampened in the whole receptor. This results in poor correlations transitioning from the NTD tetramer to the whole receptor (white dots and stippled trapezium). Also evident is a higher dominance of tetramer motions in lower-frequency modes of the NMDAR, where the tighter ECR packing restricts rearrangements in which the NTD moves as a rigid body.