Redistribution of terbium ions across acetylcholine receptor-enriched membranes induced by agonist desensitization

Thomas E. Lee, Anthony R. Chuang, Matthew S. Marek, Sebastian Doniach, Robert H Fairclough

Research output: Contribution to journalArticle

Abstract

Using small-angle x-ray diffraction from centrifugally oriented acetylcholine receptor (AChR) enriched membranes coupled with anomalous scattering from terbium ions (Tb3+) titrated into presumed Ca 2+ binding sites, we have mapped the distribution of Tb3+ perpendicular to the membrane plane using a heavy atom refinement algorithm. We have compared the distribution of Tb3+ in the closed resting state with that in the carbamylcholine-desensitized state. In the closed resting state we find 45 Tb3+ ions distributed in 10 narrow peaks perpendicular to the membrane plane. Applying the same refinement procedure to the data from carbamylcholine desensitized AChR we find 18 fewer Tb3+ ions in eight peaks, and slight rearrangements of Tb3+ density in the peaks near the ends of the AChR ion channel pore. These agonist dependent changes in the Tb3+ stoichiometry and distribution suggest a likely role for multivalent cations in stabilizing the different functional states of the AChR, and the changes in the Tb3+ distribution at the two ends of the pore suggest a potential role for multivalent cations in the gating of the ion channel.

Original languageEnglish (US)
Pages (from-to)2637-2647
Number of pages11
JournalBiophysical Journal
Volume96
Issue number7
DOIs
StatePublished - 2009

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ASJC Scopus subject areas

  • Biophysics

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