Receptor molecules, protein

As with other hormone effects, steroid hormones act by attaching to a protein receptor molecule. The fact that such small chemical differences among these basically very similar steroid molecules can result in such profoimdly different effects is just another indication of the extraordinary power of selective molecular recognition by protein molecules. Unlike the receptors for many other hormones, receptors for steroid hormones are not embedded in the cell membrane. They do not need to be because these hormone molecules are both small and hydrophobic... 

Steroid and thyroid hormones must enter their target cells to exert their effect which is manifested as a change in the pattern of protein synthesis. Steroid hormone activity (Figure 10.10b) is limited to responsive eukaryotic cells in which cytosolic protein receptor molecules are located. Thyroid hormones bind to nuclear protein receptor molecules. Steroids may enter a non-target cell by diffusion but, in the absence of appropriate receptors, depart from the cell. In target tissues, the hormone is bound to specific receptor molecules to form a steroid-receptor complex which is activated by its... 

Until now, we have discussed the use of additivity schemes to estimate global properties of a molecule such as its mean molecular polarizability, its heat of formation, or its average binding energy to a protein receptor. 

Figure 13.2 Activated G protein receptors, here represented as seven red transmembrane helices, catalyze the exchange of GTP for GDP on the Gapy trimer. The then separated Ga-GTP and Gpy molecules activate various effector molecules. The receptor is embedded in the membrane, and Ga, Gpy and G py are attached to the membrane by lipid anchors, and they all therefore move in two dimensions. (Adapted from D. Clapham, Nature 379 297-299, 1996.)...

Protein engineering is now routinely used to modify protein molecules either via site-directed mutagenesis or by combinatorial methods. Factors that are Important for the stability of proteins have been studied, such as stabilization of a helices and reducing the number of conformations in the unfolded state. Combinatorial methods produce a large number of random mutants from which those with the desired properties are selected in vitro using phage display. Specific enzyme inhibitors, increased enzymatic activity and agonists of receptor molecules are examples of successful use of this method. 

Any living cell continuously receives information about its surroundings. Its surface membrane has numerous protein receptors, which interact with practically all vitally important molecules. 

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).

Dimerization allows the kinase activity of both intracellular chains to encounter target sequences on the other, linked receptor molecule. This enables the intermolecular cross-phosphorylation of several tyrosine residues (Figure 8.2). The phosphorylated dimer then constitutes the active receptor. It possesses an array of phosphotyrosines that enable it to bind proteins to form receptor signaling complexes. Additionally, the dimerized and phosphorylated receptor has the potential of phospho-rylating its targets. 

The most fascinating aspect of the mechanism by which medicinal plants affect the brain function is their ability to elaborate molecules that are able to cross the hematoencephalic barrier and infiltrate the brain where binding to protein receptors occurs. 

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. 

Extracellular ligands (hormones, neurotrophins, carrier protein, adhesion molecules, small molecules, etc.) will bind to specific transmembrane receptors. This binding of specific ligand induces the concentration of the receptor in coated pits and internalization via clathrin-coated vesicles. One of the best studied and characterized examples of RME is the internalization of cholesterol by mammalian cells [69]. In the nervous system, there are a plethora of different membrane receptors that bind extracellular molecules, including neurotrophins, hormones and other cell modulators, being the best studied examples. This type of clathrin-mediated endocytosis is an amazingly efficient process, capable of concentrating... 

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