2M6I

Putative pentameric open-channel structure of full-length transmembrane domains of human glycine receptor alpha1 subunit

Summary for 2M6I

• Entry DOI: 10.2210/pdb2m6i/pdb
• Related: 2M6B
• NMR Information: BMRB: 19126
• Descriptor: Full-Length Transmembrane Domains of Human Glycine Receptor alpha1 Subunit (1 entity in total)
• Functional Keywords: glycine receptor, anion channel, transmembrane domain, pentamer structure, membrane protein
• Biological source: Homo sapiens
• Total number of polymer chains: 5
• Total formula weight: 86601.60

Authors

Mowrey, D.,Cui, T.,Jia, Y.,Ma, D.,Makhov, A.M.,Zhang, P.,Tang, P.,Xu, Y. (deposition date: 2013-03-29, release date: 2013-09-04, Last modification date: 2024-05-15)

Primary citation

Mowrey, D.D.,Cui, T.,Jia, Y.,Ma, D.,Makhov, A.M.,Zhang, P.,Tang, P.,Xu, Y.
Open-Channel Structures of the Human Glycine Receptor alpha 1 Full-Length Transmembrane Domain.
Structure, 21:1897-1904, 2013

PubMed Abstract: 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 α1-subunit (hGlyR-α1) using nuclear magnetic resonance (NMR) spectroscopy and electron micrographs. hGlyR-α1 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-α1 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.

PubMed: 23994010
DOI: 10.1016/j.str.2013.07.014

Experimental method

SOLUTION NMR