Figure 4: Structural basis for negative cooperativity of ligand binding to CD2 and CD3.
From: Structural basis for cpSRP43 chromodomain selectivity and dynamics in Alb3 insertase interaction
(a) Close-up view on the CD2–CD3–A3CT IV interface. Tyr319 of CD3 forms the hub of the interface. Relevant salt bridges of A3CT IV to CD2 are indicated. Arg460 is fixed on the negative helix dipole of the CD2 C-terminal helix α1. (b) Conformational changes in the CD2–CD3 interface. Top: CD2 in the cpSRP43ΔCD3–RRKRp complex. Gly316 is integral to helix α1. Bottom: CD2CD3–IV complex structure. Gly316 serves as a hinge point (indicated as sphere) and residues 316–319 form strand β2a in the CD2–CD3 interface. (c) Close-up view of NMR spectra around Gly316. In the CD3 constructs (left), Gly316 is the N-terminal residue and is located at a position common for N-terminal glycines. It shifts on A3CT titration and even more if A3CT IV is connected via a GS-linker (CD3—IV). The peak position of Gly316 changes in the CD2CD3 construct (cyan), indicating a conformational change. On binding of RRKRp (right, magenta) the lineshape improves and the peak shifts considerably indicating stabilization likely due to helix formation. Gly316 of RRKRp-preloaded CD2CD3 shifts back on addition of A3CT (cyan), according to its hinge function and the formation of strand β2a.
