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Publication Abstract from PubMed

Glycine receptors play a major role in mediating fast inhibitory neurotransmission in the spinal cord and brain stem, yet their high-resolution structures remain unsolved. We determined open-channel structures of the full-length transmembrane domain (TMD) of the human glycine receptor alpha1-subunit (hGlyR-alpha1) using nuclear magnetic resonance (NMR) spectroscopy and electron micrographs. hGlyR-alpha1 TMD spontaneously forms pentameric Cl--conducting channels, with structures sharing overall topology observed in crystal structures of homologous bacterial and nematode pentameric ligand-gated ion channels (pLGICs). However, the mammalian hGlyR-alpha1 structures present several distinctive features, including a shorter, pore-lining TM2 helix with helical unwinding near the C-terminal end, a TM3 helical kink at A288 that partially overlaps with the homologous ivermectin-binding site in GluCl, and a highly dynamic segment between S267(15') of TM2 and A288 that likely affects allosteric modulations of channel function. Our structures provide additional templates for identifying potential drug targets in GlyRs and other mammalian pLGICs.

Open-Channel Structures of the Human Glycine Receptor alpha1 Full-Length Transmembrane Domain.,Mowrey DD, Cui T, Jia Y, Ma D, Makhov AM, Zhang P, Tang P, Xu Y Structure. 2013 Aug 28. pii: S0969-2126(13)00264-5. doi:, 10.1016/j.str.2013.07.014. PMID:23994010^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.