The unanticipated complexity of the selectivity-filter glutamates of nicotinic receptors.

Nat Chem Biol

Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Published: December 2012

AI Article Synopsis

  • The study investigates a specific ring of four glutamate side chains and one glutamine in ion channels, focusing on their role in facilitating ion conduction in the muscle nicotinic acetylcholine receptor.
  • It was found that all four glutamates are deprotonated at pH levels between 6.0 and 9.0, but only two significantly affect ion current size.
  • The flexibility of these side chains is crucial, as their ability to adopt different conformations influences how effectively cations can pass through the channel, highlighting the importance of their precise location in the transmembrane pore.

Article Abstract

In ion channels, 'rings' of ionized side chains that decorate the walls of the permeation pathway often lower the energetic barrier to ion conduction. Using single-channel electrophysiological recordings, we studied the poorly understood ring of four glutamates (and one glutamine) that dominates this catalytic effect in the muscle nicotinic acetylcholine receptor ('the intermediate ring of charge'). We show that all four wild-type glutamate side chains are deprotonated in the range of 6.0-9.0 pH, that only two of them contribute to the size of the single-channel current, that these side chains must be able to adopt alternate conformations that either allow or prevent their negative charges from increasing the rate of cation conduction and that the location of these glutamate side chains squarely at one of the ends of the transmembrane pore is critical for their largely unshifted pK(a) values and for the unanticipated impact of their conformational flexibility on cation permeation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508336PMC
http://dx.doi.org/10.1038/nchembio.1092DOI Listing

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