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Reference: Wu et al EMBO J. 2000 Nov 1;19(21):5740-51 
Ribbon structure of SAP97 in a U-shaped compact conformation. Two views rotated by 90° along the imaginary axis from the PDZ1 (light blue) to the GUK (magenta) domains are shown (A). The first 48 residues of the N-terminus are missing. Identifiable structural domains, shown in different colors, include the FN type III-like domains S97N-1 (green) and S97N-2 (blue-green), PDZ1-3 (light blue, purple, blue, respectively), SH3 (white), GUK (magenta) as well as unique (U) regions. PDZ binding peptides and GMP bound to the GUK domain are shown as space filling models. The core region of U5 (Hook) and CaM binding helix (CaM) are shown in red, while the I3 insert is shown in yellow. U3 (2VSG) (pink) is predicted to form a ß-turn that forms a lid over the PDZ2 peptide binding pocket. (B) Detailed view of the U5 regions from SAP90, SAP97-I0, SAP97-I2 and SAP97-I3. The potential binding site for CaM is indicated. The core regions of U5 (helix in red and ß-turn in green) are based on the TopoII structure. In SAP97, a conserved loop is seen in all U5 elements into which the inserts are added. In I3, an additional loop is predicted to extend up and over the GUK domain. The structure of I0 closely resembles the U5 from SAP90.
Figure 7
Ribbon models of intramolecular interactions of S97N-1, SH3, U5 and GUK domains in partly dissociated SAP97. Individual domains are color coded: GUK, pink; SH3, gray; core U5, red; I3 insert, yellow; S97N-2, blue; S97N-1, light green. Space-filling model of GMP bound to the GUK domain is also shown. The models illustrate the concept of ordered assembly in which the association of one pair of domains can hinder the association of the next depending on the orders of association/dissociation placing SAP97 in a conformation that favors GKAP binding. In the sequence shown, the dissociation of I3 from GUK and S97N-1 (N-1) permits S97N-1 and then GUK to dissociate from the SH3 domain (steps 1–3). Re-association of S97N-1 with the SH3 domain would hinder the rebinding of GUK (step 4). In this configuration, U5 is prevented from interacting with S97N-1 and GUK by displacing it from its favored position. This in turn allows GKAP to bind. Binding of the I3 insert to S97N-1 at this stage (step 5) will sterically hinder the formation of a closed conformation (step 6). The conformational changes are shown as rigid body motions of the domains around the five hinge regions. These hinge regions are located between S97N-1 and S97N-2 (steps 2 and 4), between U5 and GUK (step 3), at the splice site for I3 insert (steps 1 and 5) and at the CaM binding helix (steps 3 and 5). The CaM binding helix is partly unfolded in the closed conformation, while freely accessible in the open conformation. Hence, step 6 would require two hinge motions at the same time.
