Dynamics of the acetylcholine receptor pore at the gating transition state

@article{Mitra:2005, abstract = {Neuromuscular acetylcholine receptors (AChRs) are ion channels that alternatively adopt stable conformations that either allow (open) or prohibit (closed) ionic conduction. We probed the dynamics of pore (M2) residues at the diliganded gating transition state by using single-channel kinetic and rate-equilibrium free energy relationship ({\{}Phi{\}}-value) analyses of mutant AChRs. The mutations were at the equatorial (9') position of the {\{}alpha{\}}, {\{}beta{\}}, and {\{}epsilon{\}} subunits (n = 15) or at sites between the equator and the extracellular domain in the {\{}alpha{\}}-subunit (n = 8). We also studied AChRs having only one of the two {\{}alpha{\}}-subunits mutated. The results indicate that the {\{}alpha{\}}-subunit, like the {\{}delta{\}}-subunit, has a region of flexure near the middle of M2, that the two {\{}alpha{\}}-subunits experience distinct energy barriers to gating at the equator (but not elsewhere), and that the collective subunit motions at the equator are asymmetric during the AChR gating isomerization.}, annote = {Dynamics of the acetylcholine receptor pore at the gating transition state}, author = {Mitra, A. and Cymes, G. D. and Auerbach, A. }, citeulike-article-id = {1330520}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {acetylcholinesterase, neuromuscular\_junctions}, number = {42}, pages = {15069--74}, posted-at = {2007-05-25 14:18:49}, priority = {0}, title = {Dynamics of the acetylcholine receptor pore at the gating transition state}, url = {http://dx.doi.org/10.1073/pnas.0505090102}, volume = {102}, year = {2005} }

TY - JOUR ID - Mitra:2005 L3 - citeulike-article-id:1330520 N2 - Neuromuscular acetylcholine receptors (AChRs) are ion channels that alternatively adopt stable conformations that either allow (open) or prohibit (closed) ionic conduction. We probed the dynamics of pore (M2) residues at the diliganded gating transition state by using single-channel kinetic and rate-equilibrium free energy relationship ({\{}Phi{\}}-value) analyses of mutant AChRs. The mutations were at the equatorial (9') position of the {\{}alpha{\}}, {\{}beta{\}}, and {\{}epsilon{\}} subunits (n = 15) or at sites between the equator and the extracellular domain in the {\{}alpha{\}}-subunit (n = 8). We also studied AChRs having only one of the two {\{}alpha{\}}-subunits mutated. The results indicate that the {\{}alpha{\}}-subunit, like the {\{}delta{\}}-subunit, has a region of flexure near the middle of M2, that the two {\{}alpha{\}}-subunits experience distinct energy barriers to gating at the equator (but not elsewhere), and that the collective subunit motions at the equator are asymmetric during the AChR gating isomerization. IS - 42 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 74 TI - Dynamics of the acetylcholine receptor pore at the gating transition state VL - 102 SP - 15069 KW - acetylcholinesterase KW - neuromuscular_junctions AU - Mitra, A AU - Cymes, GD AU - Auerbach, A PY - 2005/// UR - http://dx.doi.org/10.1073/pnas.0505090102 ER -