Fixation of allosteric states of the nicotinic acetylcholine receptor by chemical cross-linking
AUTOR(ES)
Watty, Anke
FONTE
The National Academy of Sciences of the USA
RESUMO
Receptor activity can be described in terms of ligand-induced transitions between functional states. The nicotinic acetylcholine receptor (nAChR), a prototypic ligand-gated ion channel, is an “unconventional allosteric protein” which exists in at least three interconvertible conformations, referred to as resting (low agonist affinity, closed channel), activated (open channel), and desensitized (high agonist affinity, closed channel). Here we show that 3,3′-dimethyl suberimidate (DMS) is an agonistic bifunctional cross-linking reagent, which irreversibly “freezes” the nAChR in a high agonist affinity/closed-channel state. The monofunctional homologue methyl acetoimidate, which is also a weak cholinergic agonist, has no such irreversible effect. Glutardialdehyde, a cross-linker that is not a cholinergic effector, fixes the receptor in a low-affinity state in the absence of carbamoylcholine, but, like DMS, in a high-affinity state in its presence. Covalent cross-linking thus allows us to arrest the nAChR in defined conformational states.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21581Documentos Relacionados
- Chemical cross-linking of Chlamydia trachomatis.
- Cross-linking reconsidered: binding and cross-linking fields and the cellular response.
- Unraveling the interface of signal recognition particle and its receptor by using chemical cross-linking and tandem mass spectrometry
- Hybridization triggered cross-linking of deoxyoligonucleotides.
- Identification of the receptor for erythropoietin by cross-linking to Friend virus-infected erythroid cells.