For example, in the nACh receptor the loop B residue Lys-145 (equivalent to Thr-179 in the 5-HT3 receptor) has been shown to form a salt-bridge with Asp-200 (Glu-236 in 5-HT3), and is proposed as one of a number of strong interactions that stabilize the binding region in this receptor (26).
The side effect is that all hydrogen bonding interactions that stabilize the Zn2+ binding site, mainly the two between N468 and C101, are weakened or lost, as shown in Figure 6.
This agreement suggests that the overall binding mechanism and the nature of the binding transition state ensemble can be understood from the network of interactions that stabilize the native fold.
This underscores the exquisite fine-tuning of interactions that stabilize the NOS dimer and the close interdependence of the Zn2+, pterin, and substrate binding sites.
Ligand binding relieves this inhibition by disrupting the L1 Fn2′ 3′ interaction that stabilizes TM separation, freeing the TMs to associate and autophosphorylation of the kinase domains to proceed.
In particular, an inter-subunit interaction that stabilizes the separation of the Fn2 3 'legs' of the ECD is disrupted by ligand binding, suggesting that TM separation may be important for maintaining the receptor in an inactive state.
The other complex, known as the microprocessor, is composed by Drosha and the DiGeorge syndrome Critical Region 8 protein (DGCR8), a dsRNA-binding protein that stabilizes Drosha through interaction with its C-terminal domain.
Autoinhibited SFK constructs (SFKSH2eng) that stabilize an αC helix-out ATP-binding site were generated by introducing mutations that strengthen intramolecular regulatory interactions between the C-terminal tail and the SH2 domain.
Inhibitors that stabilize the DFG-out and αC helix-out conformations make a number of different interactions with the ATP-binding sites of protein kinases that may account for their differing behaviors.
Here, we identify Slx9 as a RanGTP-binding protein that stabilizes the interaction between RanGTP, Rio2, and Crm1 without promoting cooperative binding between these proteins.
