Journal
BIOPHYSICAL JOURNAL
Volume 99, Issue 8, Pages 2497-2506Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2010.08.050
Keywords
-
Categories
Funding
- National Institutes of Health [NINDS 5R01NS053788]
- European Molecular Biology Organization
Ask authors/readers for more resources
Herein, we identify the coordination environment of Cu2+ in the human alpha 1-glycine receptor (GlyR). GlyRs are members of the pentameric ligand-gated ion channel superfamily (pLGIC) that mediate fast signaling at synapses. Metal ions like Zn2+ and Cu2+ significantly modulate the activity of pLGICs, and metal ion coordination is essential for proper physiological postsynaptic inhibition by GlyR in vivo. Zn2+ can either potentiate or inhibit GlyR activity depending on its concentration, while Cu2+ is inhibitory. To better understand the molecular basis of the inhibitory effect we have used electron spin resonance to directly examine Cu2+ coordination and stoichiometry. We show that Cu2+ has one binding site per alpha 1 subunit, and that five Cu2+ can be coordinated per GlyR. Cu2+ binds to E192 and H215 in each subunit of GlyR with a 40 AM apparent dissociation constant, consistent with earlier functional measurements. However, the coordination site does not include several residues of the agonist/antagonist binding site that were previously suggested to have roles in Cu2+ coordination by functional measurements. Intriguingly, the E192/H215 site has been proposed as the potentiating Zn2+ site. The opposing modulatory actions of these cations at a shared binding site highlight the sensitive allosteric nature of GlyR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available