Ligand-Receptor Interactions - Proteins

In an extensive SFA study of protein receptor-ligand interactions, Leckband and co-workers [114] showed the importance of electrostatic, dispersion, steric, and hydrophobic forces in mediating the strong streptavidin-biotin interaction. Israelachvili and co-workers [66, 115] have measured the Hamaker constant for the dispersion interaction between phospholipid bilayers and find A = 7.5 1.5 X 10 erg in water. 

ProteinChip arrays with preactivated surfaces are also available for covalently coupling of a specific bait molecule (protein, DNA, RNA). This allows the investigation of specific protein interactions such as DNA-protein, receptor-ligand, and antibody-antigen (Ab-Ag), the latter of which permits the generation of a standard curve and hence quantitation studies (21). 

This type of nanoparticle carrier assay is suitable for protein-protein, receptor-ligand, DNA-DNA and DNA-protein interactions, which makes it a versatile tool for drug discovery, cross reactivity screening, clinical diagnostics and many other applications. SchaertI and co-workers have also demonstrated... 

While the extended ternary complex model accounts for the presence of constitutive receptor activity in the absence of ligands, it is thermodynamically incomplete from the standpoint of the interaction of receptor and G-protein species. Specifically, it must be possible from a thermodynamic point of view for the inactive state receptor (ligand bound and unbound) to interact with G-proteins. The cubic ternary complex model accommodates this possibility [23-25]. From a practical point of view, it allows for the potential of receptors (whether unbound or bound by inverse agonists) to sequester G-proteins into a nonsignaling state. 

Cubic ternary complex model, a molecular model (J. Their. Biol 178, 151-167, 1996a 178, 169-182, 1996b 181, 381-397, 1996c) describing the coexistence of two receptor states that can interact with both G-proteins and ligands. The receptor/G-protein complexes may or may not produce a physiological response see Chapter 3.11. 

In the absence of specific interactions of the receptor - ligand type the change in the Helmholtz free energy (AFadj due to the process of adsorption is AFads = yps - ypi - Ysi, where Yps, YPi and ys, are the protein-solid, protein-liquid and solid-liquid interfacial tensions, respectively [5], It is apparent from this equation that the free energy of adsorption of a protein onto a surface should depend not only of the surface tension of the adhering protein molecules and the substrate material but also on the surface tension of the suspending liquid. Two different situations are possible. 

Fig. 3.4 Three models for prospective function(s) for OBPs during perireceptor delivery of a signal molecule odourant <=> protein <=> receptor site interactions could involve multiple roles. Ligand , OBP , combination(s) buffer and/or carrier and/or transducer from Pelosi, 1994).

Bouaboula M, Perrachon S, Milligan L, Canat X, Rinaldi-Carmona M, Portier M, Barth F, Calandra B, Pecceu F, Lupker J, Maffrand JP, Le Fur G, Casellas P. A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions. J Biol Chem 1997 272 22330-22339. 

Lindroos, J., M. Perakyla, J.-P. Bjorkroth, and T. A. Pakkanen. 1992. Ab Initio Models for Receptor-Ligand Interactions in Proteins. Part 1. Models for asparagine, glutamine, serine, threonine and tyrosine. J. Chem. Soc. Perkin Trans. 2, 2271-2277. 

Licitra, E. J., and Liu, J. O. (1996). A three-hybrid system for detecting small ligand—protein receptor interactions. Proc. Natl. Acad. Sci. USA 93, 12817—12821. 

As shown in Figure 6, the solvent molecules tend to be ordered around the molecules and when the protein and the ligand bind, several of these molecules are liberated and become disordered (entropic effect). Therefore, upon complex formation water molecules are released, receptor and ligand lose degrees of freedom and the interaction between the ligand and the receptor is calculated. 

The general types of protein-protein interactions that occur in cells include receptor-ligand, enzyme-substrate, multimeric complex formations, structural scaffolds, and chaperones. However, proteins interact with more targets than just other proteins. Protein interactions can include protein-protein or protein-peptide, protein-DNA/RNA or protein-nucleic acid, protein-glycan or protein-carbohydrate, protein-lipid or protein-membrane, and protein-small molecule or protein-ligand. It is likely that every molecule within a cell has some kind of specific interaction with a protein. 

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