Allosteric Communication Occurs via Networks of Tertiary and Quaternary Motions in Proteins
Figure 4
Global communication networks in three proteins.
Global communication networks (GCNs) integrate tertiary (contact rearrangement) and quaternary networks. Quaternary nodes, substrate and effector sites, quaternary interfaces, and quaternary node – ligand site interactions are represented as in Figure 2 (for lac repressor (LacR), the DNA molecules are represented as substrates). Each quaternary node is mapped to its position in the three-dimensional structure of the active state (1EFA for LacR and 1PJ2 for malic enzyme) by the node's outline color (see Figure 2 for the mapping for PFK). Tertiary nodes comprising 10 or more residues or contacting a ligand site are represented as octagons with the area proportional to the number of residues; these nodes are numbered by size from largest to smallest. In addition, in lac repressor, square nodes represent segments present only in the active state structure. Modifications to both tertiary and quaternary node areas have been made to account for the participation of some residues in both tertiary and quaternary nodes. Quaternary node-tertiary node edges indicate intersections (shared residues) between these two types of nodes, and an edge between a tertiary node and a ligand site indicates that the ligand site participates in the CRN cluster corresponding to the tertiary node. Furthermore, for malic enzyme, grey dashed lines mark the allosteric unit boundaries (for both PFK and lac repressor, the entire protein is the allosteric unit). Finally, the density of dashing of a quaternary edge is proportional to the interfacial contact rearrangement fCR. Solid: fCR<10% (conserved interface); dashed: 10%≤fCR≤50% (moderately rearranged); dotted: fCR>50% (extensively rearranged). See the methods for the full details of the GCN representation and associated calculations. Graphs drawn by yEd graph editor. Specific residues comprised by each quaternary node are available in Dataset S1.