The contribution of proline 250 (P-2') to pore diameter and ion selectivity in the human glycine receptor channel.
The glycine receptor-channel (GlyR) mediates neuronal inhibition by selectively allowing the passage of Cl(-) ions through its channel. The pore region for ion selectivity is localised to the constricted internal end of the M2 transmembrane domain. This paper investigates the contribution of the P-2' residue in determining pore diameter and ion charge selectivity of the GlyR. The deletion of this proline has been shown to decrease the anion/cation permeability ratio, with P(Cl)/P(Na) decreasing from approximately 27 to approximately 4. We show that the P-2' deletion by itself produces a GlyR with a larger pore diameter ( approximately 0.69 nm) than the wild type value ( approximately 0.54 nm). This confirms that the P-2' residue reduces pore size, which suggests that, in addition to electrostatic effects, pore size also contributes to ion-charge selectivity.
Lee
David J-S
DJ
Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Keramidas
Angelo
A
Moorhouse
Andrew J
AJ
Schofield
Peter R
PR
Barry
Peter H
PH
D000595:Amino Acid Sequence; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011392:Proline / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D018009:Receptors, Glycine / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D018009:Receptors, Glycine; D011392:Proline