3GUA

Sulfates bound in the vestibule of AChBP

Summary for 3GUA

• Entry DOI: 10.2210/pdb3gua/pdb
• Descriptor: Soluble acetylcholine receptor, SULFATE ION (3 entities in total)
• Functional Keywords: ion channel, ion selectivity, ion filter, receptor, choline-binding protein
• Biological source: Aplysia californica (California sea hare)
• Total number of polymer chains: 10
• Total formula weight: 249292.16

Authors

Hansen, S.B.,Taylor, P. (deposition date: 2009-03-28, release date: 2009-07-14, Last modification date: 2024-11-06)

Primary citation

Hansen, S.B.,Wang, H.L.,Taylor, P.,Sine, S.M.
An Ion Selectivity Filter in the Extracellular Domain of Cys-loop Receptors Reveals Determinants for Ion Conductance
J.Biol.Chem., 283:36066-36070, 2008

PubMed 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.

PubMed: 18940802
DOI: 10.1074/jbc.C800194200

Experimental method

X-RAY DIFFRACTION (3.1 Å)