Energy and Structure of the M2 Helix in Acetylcholine Receptor-Channel Gating
AUTOR(ES)
Jha, Archana
FONTE
The Biophysical Society
RESUMO
We studied single-channel currents from neuromuscular acetylcholine receptor-channels with mutations in the pore-lining, M2 helix of the ɛ-subunit. Three parameters were quantified: 1), the diliganded gating equilibrium constant (E2), which reflects the energy difference between C(losed) and O(pen) conformations; 2), the correlation between the opening rate constant and E2 on a log-log scale (Φ), which illuminates the energy character of the residue (C- versus O-like) within the C↔O isomerization process; and 3), the open-channel current amplitude (i0), which reports whether a mutation alters the energetics of ion permeation. The largest E2 changes were observed in the cytoplasmic half of ɛM2 (5′, 9′, 12′, 13′, and 16′), with smaller changes apparent for residues ≥17′. Φ was ∼0.54 for most ɛM2 residues, but was ∼0.32 at the positions that had largest E2 changes. An arginine substitution reduced i0 significantly at six positions, with the magnitude of the reduction increasing, 16′→2′. The measurements suggest that the 9′, 12′, and 13′ residues experience large and late free-energy changes in the channel-opening process. We speculate that in the gating isomerization the pore-facing residues >6′ and <16′ experience multiple energy perturbations associated with changes in protein structure and, perhaps, hydration.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2712209Documentos Relacionados
- Monovalent cation conductance in the ryanodine receptor-channel of sheep cardiac muscle sarcoplasmic reticulum.
- Some characteristics of the functioning of membrane receptor-channel complexes of Limnaea stagnalis neurones.
- Photolabeling reveals the proximity of the alpha-neurotoxin binding site to the M2 helix of the ion channel in the nicotinic acetylcholine receptor.
- Noradrenaline modulates calcium channels in avian dorsal root ganglion cells through tight receptor-channel coupling.
- N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex.