Preferential assembly of heteromeric kainate and AMPA receptor amino terminal domains
Ion conductivity and the gating characteristics of tetrameric glutamate receptor ion channels are determined by their subunit composition. Competitive homo- and hetero-dimerization of their amino-terminal domains (ATDs) is a key step controlling assembly. Here we measured systematically the thermodynamic stabilities of homodimers and heterodimers of kainate and AMPA receptors using fluorescence-detected sedimentation velocity analytical ultracentrifugation. Measured affinities span many orders of magnitude, and complexes show large differences in kinetic stabilities. The association of kainate receptor ATD dimers is generally weaker than the association of AMPA receptor ATD dimers, but both show a general pattern of increased heterodimer stability as compared to the homodimers of their constituents, matching well physiologically observed receptor combinations. The free energy maps of AMPA and kainate receptor ATD dimers provide a framework for the interpretation of observed receptor subtype combinations and possible assembly pathways.
Article and author information
National Institutes of Health (ZIA EB000008-11)
- Peter Schuck
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Gary L Westbrook, Vollum Institute, United States
- Received: September 15, 2017
- Accepted: October 22, 2017
- Accepted Manuscript published: October 23, 2017 (version 1)
- Accepted Manuscript updated: October 25, 2017 (version 2)
- Version of Record published: November 1, 2017 (version 3)
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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