The energetic consequences of loop 9 gating motions in acetylcholine receptor-channels

Archana Jha, Shaweta Gupta, Shoshanna N. Zucker, Anthony Auerbach

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Abstract

Acetylcholine receptor-channels (AChRs) mediate fast synaptic transmission between nerve and muscle. In order to better-understand the mechanism by which this protein assembles and isomerizes between closed- and open-channel conformations we measured changes in the diliganded gating equilibrium constant (E 2) consequent to mutations of residues at the C-terminus of loop 9 (L9) in the α and e{open} subunits of mouse neuromuscular AChRs. These amino acids are close to two interesting interfaces, between the extracellular and transmembrane domain within a subunit (E-T interface) and between primary and complementary subunits (P-C interface). Most α subunit mutations modestly decreased E 2 (mainly by slowing the channel-opening rate constant) and sometimes produced AChRs that had heterogeneous gating kinetic properties. Mutations in the e{open} subunit had a larger effect and could either increase or decrease E 2, but did not induce kinetic heterogeneity. There are broad-but-weak energetic interactions between αL9 residues and others at the αE-T interface, as well as between the e{open}L9 residue and others at the P-C interface (in particular, the M2-M3 linker). These interactions serve, in part, to maintain the structural integrity of the AChR assembly at the E-T interface. Overall, the energy changes of L9 residues are significant but smaller than in other regions of the protein.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalJournal of Physiology
Volume590
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

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All Science Journal Classification (ASJC) codes

  • Physiology

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