Binding site of AChR: Difference between revisions
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The X-ray structure of AChR has not yet been solved since its hydrophobic character hampers its successful crystallization. So in this page,<ref>PMID:11683996</ref> We will use a complex of α-bungarotoxinwith a high affinity 13-residue peptide that is homologous to the αsubunit of AChR to study the AChR binding site in general. We also will present the [http://proteopedia.org/wiki/index.php/Acetylcholine_binding_protein Acetylcholine binding protein] and the general [http://proteopedia.org/wiki/index.php/4hfi pentameric ligand gated ion channels] to help you understand this kind of structure and their function. | The X-ray structure of AChR has not yet been solved since its hydrophobic character hampers its successful crystallization. So in this page,<ref>PMID:11683996</ref> We will use a complex of α-bungarotoxinwith a high affinity 13-residue peptide that is homologous to the αsubunit of AChR to study the AChR binding site in general. We also will present the [http://proteopedia.org/wiki/index.php/Acetylcholine_binding_protein Acetylcholine binding protein] and the general [http://proteopedia.org/wiki/index.php/4hfi pentameric ligand gated ion channels] to help you understand this kind of structure and their function. | ||
Nicotinic receptors, with a molecular mass of 290 kDa,<ref>PMID:15701510</ref> are made up of five subunits, arranged symmetrically around a central pore.Each subunit comprises four transmembrane domains with both the N- and C-terminus located extracellularly. | Nicotinic receptors, with a molecular mass of 290 kDa,<ref>PMID:15701510</ref> are made up of five subunits, arranged symmetrically around a central pore.Each subunit comprises four transmembrane domains with both the N- and C-terminus located extracellularly.So as with all ligand-gated ion channels, opening of the nAChR channel pore requires the binding of a chemical messenger.Several different terms are used to refer to the molecules that bind receptors, such as ligand. As well as the endogenous agonist acetylcholine, agonists of the nAChR are nicotine, epibatidine, and choline. | ||
In muscle-type nAChRs, the acetylcholine binding sites are located at the α and either ε or δ subunits interface (or between two α subunits in the case of homomeric receptors) in the extracellular domain near the N terminus.When an agonist binds to the site, all present subunits undergo a conformational change and the channel is opened<ref>PMID:15165738</ref> and a pore with a diameter of about 0.65 nm opens. | In muscle-type nAChRs, the acetylcholine binding sites are located at the α and either ε or δ subunits interface (or between two α subunits in the case of homomeric receptors) in the extracellular domain near the N terminus.When an agonist binds to the site, all present subunits undergo a conformational change and the channel is opened<ref>PMID:15165738</ref> and a pore with a diameter of about 0.65 nm opens. | ||
Nicotinic AChRs may exist in different interconvertible conformational states. Binding of an agonist stabilises the open and desensitised states. Opening of the channel allows positively charged ions to move across it; in particular, sodium enters the cell and potassium exits. The net flow of positively-charged ions is inward. | Nicotinic AChRs may exist in different interconvertible conformational states. Binding of an agonist stabilises the open and desensitised states. Opening of the channel allows positively charged ions to move across it; in particular, sodium enters the cell and potassium exits. The net flow of positively-charged ions is inward.The nAChR is a non-selective cation channel, meaning that several different positively charged ions can cross through.It is permeable to Na+ and K+, with some subunit combinations that are also permeable to Ca2+<ref>PMID:12761283</ref><ref>PMID:15644873</ref> The amount of sodium and potassium the channels allow through their pores (their conductance) varies from 50–110 pS, with the conductance depending on the specific subunit composition as well as the permeant ion.<ref>PMID:2423878</ref> | ||
The nAChR is a non-selective cation channel, meaning that several different positively charged ions can cross through.It is permeable to Na+ and K+, with some subunit combinations that are also permeable to Ca2+<ref>PMID:12761283</ref><ref>PMID:15644873</ref> The amount of sodium and potassium the channels allow through their pores (their conductance) varies from 50–110 pS, with the conductance depending on the specific subunit composition as well as the permeant ion.<ref>PMID:2423878</ref> | |||
The nAChR is unable to bind ACh when bound to any of the snake venom α-neurotoxins. These α-neurotoxins antagonistically bind tightly and noncovalently to nAChRs of skeletal muscles, thereby blocking the action of ACh at the postsynaptic membrane, inhibiting ion flow and leading to paralysis and death. The nAChR contains two binding sites for snake venom neurotoxins. Some studies have shown that a twist-like motion caused by ACh binding is likely responsible for pore opening, and that one or two molecules of α-bungarotoxin (or other long-chain α-neurotoxin) suffice to halt this motion. The toxins seem to lock together neighboring receptor subunits, inhibiting the twist and therefore, the opening motion.<ref>PMID:18327915</ref> | The nAChR is unable to bind ACh when bound to any of the snake venom α-neurotoxins. These α-neurotoxins antagonistically bind tightly and noncovalently to nAChRs of skeletal muscles, thereby blocking the action of ACh at the postsynaptic membrane, inhibiting ion flow and leading to paralysis and death. The nAChR contains two binding sites for snake venom neurotoxins. Some studies have shown that a twist-like motion caused by ACh binding is likely responsible for pore opening, and that one or two molecules of α-bungarotoxin (or other long-chain α-neurotoxin) suffice to halt this motion. The toxins seem to lock together neighboring receptor subunits, inhibiting the twist and therefore, the opening motion.<ref>PMID:18327915</ref> | ||