Receptor-protein interaction

The interest in vesicles as models for cell biomembranes has led to much work on the interactions within and between lipid layers. The primary contributions to vesicle stability and curvature include those familiar to us already, the electrostatic interactions between charged head groups (Chapter V) and the van der Waals interaction between layers (Chapter VI). An additional force due to thermal fluctuations in membranes produces a steric repulsion between membranes known as the Helfrich or undulation interaction. This force has been quantified by Sackmann and co-workers using reflection interference contrast microscopy to monitor vesicles weakly adhering to a solid substrate [78]. Membrane fluctuation forces may influence the interactions between proteins embedded in them [79]. Finally, in balance with these forces, bending elasticity helps determine shape transitions [80], interactions between inclusions [81], aggregation of membrane junctions [82], and unbinding of pinched membranes [83]. Specific interactions between membrane embedded receptors add an additional complication to biomembrane behavior. These have been stud-... 

Mode of Motion. Nicotine, anabasine, and imidocloprid affect the ganglia of the insect central nervous system, faciUtating transsynaptic conduction at low concentrations and blocking conduction at higher levels. The extent of ionisation of the nicotinoids plays an important role in both their penetration through the ionic barrier of the nerve sheath to the site of action and in their interaction with the site of action, which is befleved to be the acetylcholine receptor protein. There is a marked similarity in dimensions between acetylcholine and the nicotinium ion. 

While some biological targets such as DNA are not protein in nature, most receptors are. It is useful to consider the properties of receptor proteins to provide a context for the interaction of small molecule drugs with them. An important property of receptors is that they have a 3D structure. Proteins usually are comprised of one or... 

Antagonist, a molecule that interferes with the interaction of an agonist and a receptor protein or a molecule that blocks the constitutive elevated basal response of a physiological system. 

Table Appendix Receptor Proteins Drug-Receptor Interaction... 

Transmembrane Signaling Drag-receptor Interaction G-protein-coupled Receptors Histaminergic System Adenosine Receptois... 

Drug Interactions Drug-Receptor Interaction G-protein-coupled Receptors Tolerance and Desensitization Transmembrane Signaling... 

PTKs can be subdivided into two large families, receptor tyrosine kinases (RTKs) and non-RTKs. The human genome encodes for a total of 90 tyrosine kinases of which 32 are nonreceptor PTKs that can be placed in 10 subfamilies (Fig. 1). All nonreceptor PTKs share a common kinase domain and usually contain several additional domains that mediate interactions with protein-binding partners, membrane lipids, or DNA (Table 1). These interactions may affect cellular localization and the activation status of the kinase or attract substrate proteins for phosphorylation reactions. 

While it has been known for many years that the N-terminal presequence is sufficient to promote mitochondrial targeting and assembly, the subsequent interaction of the precursor molecule with the outer mitochondrial membrane and the uptake of the protein is still an area of active research. There seems little doubt, however, that there are proteins on the outer mitochondrial membrane which are required for the import process. The function of these proteins is uncertain, but they may act as receptors with the subsequent transfer through the membrane at proteinous pores located at contact sites between the inner and outer membranes. Several proteins have been identified which seem to play an important role as either receptor proteins or part of the import channel (Pfanner et al., 1991). Again, not all proteins seem to depend on this mechanism. Cytochrome c, which is loosely associated with the outer aspect of the inner mitochondrial membrane, can cross... 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

This sequence specifies that such proteins will be attached to the inner aspect of the ER in a relatively loose manner. The chaperone BiP (see below) is one such protein. Actually, KDEL-containing proteins first travel to the Golgi, interact there with a specific KDEL receptor protein, and then return in transport vesicles to the ER, where they dissociate from the receptor. 

Binding of these ligands does not occur in a concave groove located on the surface of the receptor protein as otherwise often imagined. As described in Section 2.2.1, the x-ray structure of rhodopsin showed that retinal is bound deep in the seven-helical structure with major interaction points in TM-III and TM-VI, as well as the covalent attachment point in TM-VII. In fact, rhodopsin interacts with basically all transmembrane segments. Importantly, side-chains from the transmembrane helices cover the retinal molecule on all sides, and its binding site is found deep in the middle of... 

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