Conformation change ligand induced

To generate an optimal fit for the antigen, the binding sites of IgG often undergo slight conformational changes. Such induced fit is common to many protein-ligand interactions. 

Van Aalten, D.M.F., Findlay, J.B.C., Amadei, A., Berendsen,H.J.C. Essential dynamics of the cellular retinol-binding protein. Evidence for ligand-induced conformational changes. Protein Engin. 8 (1995) 1129-1136. 

The elegant genetic studies by the group of Charles Yanofsky at Stanford University, conducted before the crystal structure was known, confirm this mechanism. The side chain of Ala 77, which is in the loop region of the helix-turn-helix motif, faces the cavity where tryptophan binds. When this side chain is replaced by the bulkier side chain of Val, the mutant repressor does not require tryptophan to be able to bind specifically to the operator DNA. The presence of a bulkier valine side chain at position 77 maintains the heads in an active conformation even in the absence of bound tryptophan. The crystal structure of this mutant repressor, in the absence of tryptophan, is basically the same as that of the wild-type repressor with tryptophan. This is an excellent example of how ligand-induced conformational changes can be mimicked by amino acid substitutions in the protein. 

Natural or synthethic receptor ligands that induce a conformational change (active conformation) and a signal transduction process upon receptor binding. Agonists may act as typical hormones or neurotransmitters or they may confer paracrine functions, recognize bacterial, viral or other environmental constituents via activating their dedicated receptors. 

In the case of liganded NRs, ligand binding is the first and ciucial molecular event that switches the function of these transcription factors from inactive to active state by inducing a conformational change in the LBD of the receptor (Fig. 1). This specific conformation allows the second step of NR activation that corresponds to the recruitment of coregulatoiy complexes, which contain chromatin-modifying enzymes required for transcription. The transcriptional coactivators are very diverse and have expanded to more than hundred in number. These include the pi 60 family of proteins,... 

---