RGD Reference Report - Single-channel behavior of heteromeric alpha1beta glycine receptors: an attempt to detect a conformational change before the channel opens. - Rat Genome Database

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Single-channel behavior of heteromeric alpha1beta glycine receptors: an attempt to detect a conformational change before the channel opens.

Authors: Burzomato, V  Beato, M  Groot-Kormelink, PJ  Colquhoun, D  Sivilotti, LG 
Citation: Burzomato V, etal., J Neurosci. 2004 Dec 1;24(48):10924-40.
RGD ID: 1598572
Pubmed: PMID:15574743   (View Abstract at PubMed)
PMCID: PMC6730200   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3424-04.2004   (Journal Full-text)

The alpha1beta heteromeric receptors are likely to be the predominant synaptic form of glycine receptors in the adult. Their activation mechanism was investigated by fitting putative mechanisms to single-channel recordings obtained at four glycine concentrations (10-1000 microm) from rat alpha1beta receptors, expressed in human embryonic kidney 293 cells. The adequacy of each mechanism, with its fitted rate constants, was assessed by comparing experimental dwell time distributions, open-shut correlations, and the concentration-open probability (P(open)) curve with the predictions of the model. A good description was obtained only if the mechanism had three glycine binding sites, allowed both partially and fully liganded openings, and predicted the presence of open-shut correlations. A strong feature of the data was the appearance of an increase in binding affinity as more glycine molecules bind, before the channel opens. One interpretation of this positive binding cooperativity is that binding sites interact, each site sensing the state of ligation of the others. An alternative, and novel, explanation is that agonist binding stabilizes a higher affinity form of the receptor that is produced by a conformational change ("flip") that is separate from, and precedes, channel opening. Both the "interaction" scheme and the flip scheme describe our data well, but the latter has fewer free parameters and above all it offers a mechanism for the affinity increase. Distinguishing between the two mechanisms will be important for our understanding of the structural dynamics of activation in the nicotinic superfamily and is important for our understanding of mutations in these receptors.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Glra1Ratsynaptic transmission, glycinergic  IDA  RGD 
GlrbRatsynaptic transmission, glycinergic  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Glra1Ratextracellularly glycine-gated ion channel activity  IDA  RGD 
GlrbRatextracellularly glycine-gated ion channel activity  IDA  RGD 
Glra1Ratglycine binding  IDA  RGD 
GlrbRatglycine binding  IDA  RGD 
Glra1Ratprotein-containing complex binding  IDA heterooligomerizationRGD 
GlrbRatprotein-containing complex binding  IDA heterooligomerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Glra1  (glycine receptor, alpha 1)
Glrb  (glycine receptor, beta)


Additional Information