Neuronal receptors structure

Jensen AA, Frolund B, Liljefors T et al (2005) Neuronal nicotinic acetylcholine receptors structural revelations, target identifications, and therapeutic inspirations. J Med Chem 48 4705—4745... 

It is interesting that the stimulus compounds used in the study differ widely in their molecular structures, and yet they all interact with antibodies to thaumatin. It is, therefore, probable that a single receptor-structure responds to all sweet stimuli,there being a variation in the relative effectiveness of sweet stimuli across individual nerve-fibers, and the characteristics of all receptor sites do not appear to be identical. Earlier elec-trophysiological studies of single primary, afferent taste-neurons uniformly agreed that individual fibers very often have multiple sensitivities, and that individual, gustatory receptors are part of the receptive field of more than one afferent fiber. " We have yet to learn how these interact, and the nature of their excitatory, or possible inhibitory, relations, or both. 

Alirezaei M, Watry DD, Flynn CF, Kiosses WB, MasUah E, Williams BR, Kaul M, Lipton SA, Fox HS (2007) Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signahng in neurons. J Neurosci 27 11047-11055 Allen SJ, Crown SE, Handel TM (2007) Chemokine receptor structure, interactions, and antagonism. Annu Rev Immunol 25 787-820... 

The molecular nature of the neuronal receptors is now becoming understood with the advent of molecular biological techniques. The molecular structure of the mechanosensitive channels has been established only recently. In principle mechanosensitive channels must be opened by mechanical deformation of the neural membrane in which they are em-... 

Nicotinic receptors are of the ionotropic type which, on stimulation by acetylcholine, nicotine or related agonists, open to allow the passage of sodium ions into the neuron. There are structural differences between the peripheral and neuronal receptors, the former being pentamers composed of two alpha and one beta, gamma and delta sub-units while the latter consist of single alpha and beta sub-units. It is now known that there are at least four variants of the alpha and two of the beta sub-units in the brain. In Alzheimer s disease it would appear that there is a selective reduction in the nicotinic receptors which contain the alpha 3 and 4 sub-units (Figure 2.9). 

Fig. 1. Example of a receptor structure. Some anti-epileptic drugs interact with a receptor site on a Na" " channel and enhance the activity of the inactivation gate (I) decreasing the ahihty of neurons to fire at high frequencies. (A) indicates the activation gate of this ion channel. (Reprinted by permission from McNamara JO. Emerging insights into the genesis of epilepsy. Nature 1999 399(Suppl) A15-22, 1999 Macmillan Magazines Ltd.)...

Kuryatov, A., Laube, B., Betz, H., Kuhse, J. Mutational analysis of the glycine binding site of the NMDA receptor Structural similiarity with bacterial amino acid binding proteins, Neuron 1994, 12, 1291-1300. 

FIGURE 1 — 3. The synapse is enlarged conceptually here showing its specialized structures that enable chemical neurotransmission to occur. Specifically, a presynaptic neuron sends its axon terminal to form a synapse with a postsynaptic neuron. Energy for this process is provided by mitochondria in the presynaptic neuron. Chemical neurotransmitter is stored in small vesicles ready for release on firing of the presynaptic neuron. The synaptic cleft is the connection between the presynaptic neuron and the postsynaptic neuron. Receptors are present on both sides of this cleft and are key elements of chemical neurotransmission. 

STRUCTURES OF AXON GUIDANCE MOLECULES AND THEIR NEURONAL RECEPTORS... 

Structure-activity studies suggested pheromones were detected by receptor proteins [37, 38], and chemicals that disrupt protein structure had been used to uncouple odour response pathways [39, 40], In 1974, Karl-Emst Kaissling [41] proposed a model for pheromone detection in silk moths in which pheromone molecules were transported to neuronal receptor proteins via pore-tubules [42, 43] and were subsequently inactivated by some rapid non-enzymatic process. 

The premier components of venom of cone snails are the conotoxins. Most conotoxins contain either two or three disulfide bonds. Several conotoxin frameworks constrained in a variety of patterns (including knotting) have been identified (Table 1). Multiple disulfide bonds provide conotoxins with unusual structural stability that makes them difficult to degrade, as they typically cannot unfold with the same ease as their nonconstrained counterparts. Furthermore, location of Cys residues along the sequence and disulfide pairing impart additional structural diversity, which allows conotoxins to effectively target a vast array of different ion channels and G-protein-coupled neuronal receptors present in their prey organisms. 

There is an intimate relationship between the conopeptide type, its structure, and its selectivity different types of conopeptides target different neuronal receptor types. However, with the same conopeptide type (or subtypes), selectivity varies tremendously, as different sites within the same receptor can be targeted by the conopeptides whose difference is only one amino acid. This is illustrated by the selectivity of a-conotoxins (Table 3) toward the nAChR. This is further augmented by a new level of conotoxin diversity, as a nonnative disulfide bond connectivity in a-conotoxin AuIB reduces structural definition but increases biological activity. ... 

Structures of Axon Guidance Molecules and their Neuronal Receptors... 

Jammes Y, Fomaris E, Mei N, Barrat E (1982) Afferent and efferent components of the bronchial vagal branches in cats. J Auton Nerv Syst 5 165-176 Jensen AA, Erolund B, Ldjefors T, Krogsgaard-Larsen P (2005) Neuronal nicotinic acetylchohne receptors Structural revelations, target identifications, and therapeutic inspirations. J Med Chem 48 4705-4745... 

---