TY - JOUR
T1 - Conserved quaternary structure of ligand-gated ion channels
T2 - The postsynaptic glycine receptor is a pentamer
AU - Langosch, D.
AU - Thomas, L.
AU - Betz, H.
PY - 1988
Y1 - 1988
N2 - The postsynaptic glycine receptor of rat spinal cord is a glycosylated membrane protein that, after affinity purification, contains membrane-spanning subunits of M(r) 48,000 and 58,000 and an associated peripheral polypeptide of M(r) 93,000. Here, the quaternary structure of the transmembrane core of the receptor was investigated by chemically crosslinking its subunits. Upon treatment with crosslinking reagents of different side-chain specificities and lengths, a consistent set of adducts up to M(r) 260,000 was detected after separation by NaDodSO4/PAGE. The observed pattern of adducts was similar irrespective of whether purified receptor protein or synaptosomal membranes were crosslinked. Compositional analysis revealed that the crosslinked adducts contained the M(r) 48,000 and 58,000 subunits in varying ratios but not the peripheral M(r) 93,000 polypeptide. Thus adducts of intermediate molecular weight represent dimers, trimers, and tetramers of the transmembrane subunits, whereas the major adduct of M(r) 260,000 corresponds to a pentameric assembly of subunits forming the ion channel of the glycine receptor. This subunit arrangement is similar to that reported for the nicotinic acetylcholine receptor of fish electric organ and skeletal muscle. Hence, we suggest that the different ligand-gated ion channels of excitable membranes share a similar quaternary structure.
AB - The postsynaptic glycine receptor of rat spinal cord is a glycosylated membrane protein that, after affinity purification, contains membrane-spanning subunits of M(r) 48,000 and 58,000 and an associated peripheral polypeptide of M(r) 93,000. Here, the quaternary structure of the transmembrane core of the receptor was investigated by chemically crosslinking its subunits. Upon treatment with crosslinking reagents of different side-chain specificities and lengths, a consistent set of adducts up to M(r) 260,000 was detected after separation by NaDodSO4/PAGE. The observed pattern of adducts was similar irrespective of whether purified receptor protein or synaptosomal membranes were crosslinked. Compositional analysis revealed that the crosslinked adducts contained the M(r) 48,000 and 58,000 subunits in varying ratios but not the peripheral M(r) 93,000 polypeptide. Thus adducts of intermediate molecular weight represent dimers, trimers, and tetramers of the transmembrane subunits, whereas the major adduct of M(r) 260,000 corresponds to a pentameric assembly of subunits forming the ion channel of the glycine receptor. This subunit arrangement is similar to that reported for the nicotinic acetylcholine receptor of fish electric organ and skeletal muscle. Hence, we suggest that the different ligand-gated ion channels of excitable membranes share a similar quaternary structure.
UR - http://www.scopus.com/inward/record.url?scp=0001202076&partnerID=8YFLogxK
U2 - 10.1073/pnas.85.19.7394
DO - 10.1073/pnas.85.19.7394
M3 - Article
C2 - 2459705
AN - SCOPUS:0001202076
SN - 0027-8424
VL - 85
SP - 7394
EP - 7398
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -