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Functional anatomy of an allosteric protein.

ABSTRACT: Synaptic receptors are allosteric proteins that switch on and off to regulate cell signalling. Here, we use single-channel electrophysiology to measure and map energy changes in the gating conformational change of a nicotinic acetylcholine receptor. Two separated regions in the ?-subunits--the transmitter-binding sites and ?M2-?M3 linkers in the membrane domain--have the highest ?-values (change conformation the earliest), followed by the extracellular domain, most of the membrane domain and the gate. Large gating-energy changes occur at the transmitter-binding sites, ?-subunit interfaces, the ?M1 helix and the gate. We hypothesize that rearrangements of the linkers trigger the global allosteric transition, and that the hydrophobic gate unlocks in three steps. The mostly local character of side-chain energy changes and the similarly high ?-values of separated domains, both with and without ligands, suggest that gating is not strictly a mechanical process initiated by the affinity change for the agonist.

SUBMITTER: Purohit P

PROVIDER: S-EPMC4407639 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Functional anatomy of an allosteric protein.

Purohit Prasad P Gupta Shaweta S Jadey Snehal S Auerbach Anthony A

Nature communications 20130101

Synaptic receptors are allosteric proteins that switch on and off to regulate cell signalling. Here, we use single-channel electrophysiology to measure and map energy changes in the gating conformational change of a nicotinic acetylcholine receptor. Two separated regions in the α-subunits--the transmitter-binding sites and αM2-αM3 linkers in the membrane domain--have the highest ϕ-values (change conformation the earliest), followed by the extracellular domain, most of the membrane domain and the ...[more]

PMID: 24352193

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