Back to Search
Start Over
An ion selectivity filter in the extracellular domain of Cys-loop receptors reveals determinants for ion conductance.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2008 Dec 26; Vol. 283 (52), pp. 36066-70. Date of Electronic Publication: 2008 Oct 21. - Publication Year :
- 2008
-
Abstract
- Neurotransmitter binding to Cys-loop receptors promotes a prodigious transmembrane flux of several million ions/s, but to date, structural determinants of ion flux have been identified flanking the membrane-spanning region. Using x-ray crystallography, sequence analysis, and single-channel recording, we identified a novel determinant of ion conductance near the point of entry of permeant ions. Co-crystallization of acetylcholine-binding protein with sulfate anions revealed coordination of SO4(2-) with a ring of lysines at a position equivalent to 24 A above the lipid membrane in homologous Cys-loop receptors. Analysis of multiple sequence alignments revealed that residues equivalent to the ring of lysines are negatively charged in cation-selective receptors but are positively charged in anion-selective receptors. Charge reversal of side chains at homologous positions in the nicotinic receptor from the motor end plate decreases unitary conductance up to 80%. Selectivity filters stemming from transmembrane alpha-helices have similar pore diameters and compositions of amino acids. These findings establish that when the channel opens under a physiological electrochemical gradient, permeant ions are initially stabilized within the extracellular vestibule of Cys-loop receptors, and this stabilization is a major determinant of ion conductance.
- Subjects :
- Amino Acid Sequence
Animals
Cell Membrane metabolism
Crystallography, X-Ray methods
Cytoplasm metabolism
Humans
Models, Biological
Molecular Conformation
Molecular Sequence Data
Protein Structure, Secondary
Protein Structure, Tertiary
Receptors, Nicotinic chemistry
Sequence Homology, Amino Acid
Cysteine chemistry
Ions
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 283
- Issue :
- 52
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18940802
- Full Text :
- https://doi.org/10.1074/jbc.C800194200