| First Author | Purohit P | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 24 | Pages | 9384-9 |
| PubMed ID | 22647603 | Mgi Jnum | J:185517 |
| Mgi Id | MGI:5429103 | Doi | 10.1073/pnas.1203633109 |
| Citation | Purohit P, et al. (2012) Sources of energy for gating by neurotransmitters in acetylcholine receptor channels. Proc Natl Acad Sci U S A 109(24):9384-9 |
| abstractText | Nicotinic acetylcholine receptors (AChRs) mediate signaling in the central and peripheral nervous systems. The AChR gating conformational change is powered by a low- to high-affinity change for neurotransmitters at two transmitter binding sites. We estimated (from single-channel currents) the components of energy for gating arising from binding site aromatic residues in the alpha-subunit. All mutations reduced the energy (TyrC1>>TrpB approximately TyrC2>TyrA), with TyrC1 providing approximately 40% of the total. Considered one at a time, the fractional energy contributions from the aromatic rings were TrpB approximately 35%, TyrC1 approximately 28%, TyrC2 approximately 28%, and TyrA approximately 10%. Together, TrpB, TyrC1, and TyrC2 comprise an "aromatic triad" that provides much of the total energy from the transmitter for gating. Analysis of mutant pairs suggests that the energy contributions from some residues are nearly independent. Mutations of TyrC1 cause particularly large energy reductions because they remove two favorable and approximately equal interactions between the aromatic ring and the quaternary amine of the agonist and between the hydroxyl and alphaLysbeta7. |
