A prokaryotic glutamate receptor: homology modelling and molecular dynamics simulations of GluR0.
GluR0 is a prokaryotic homologue of mammalian glutamate receptors that forms glutamate-activated, potassium-selective ion channels. The topology of its transmembrane (TM) domain is similar to that of simple potassium channels such as KcsA. Two plausible alignments of the sequence of the TM domain of GluR0 with KcsA are possible, differing in the region of the P helix. We have constructed homology models based on both alignments and evaluated them using 6 ns duration molecular dynamics simulations in a membrane-mimetic environment. One model, in which an insertion in GluR0 relative to KcsA is located in the loop between the M1 and P helices, is preferred on the basis of lower structural drift and maintenance of the P helix conformation during simulation. This model also exhibits inter-subunit salt bridges that help to stabilise the TM domain tetramer. During the simulation, concerted K(+) ion-water movement along the selectivity filter is observed, as is the case in simulations of KcsA. K(+) ion exit from the central cavity is associated with opening of the hydrophobic gate formed by the C-termini of the M2 helices. In the intact receptor the opening of this gate will be controlled by interactions with the extramembranous ligand-binding domains.
Department of Biochemistry, The University of Oxford, The Rex Richards Building, South Parks Road, OX1 3QU Oxford, UK.
Yalini
Y
Arinaminpathy
Philip C
PC
Biggin
Indira H
IH
Shrivastava
Mark S P
MS
Sansom
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology; D001665:Binding Sites; D003198:Computer Simulation; D015640:Ion Channel Gating / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000502:physiology; D011387:Prokaryotic Cells / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D008565:Membrane Proteins; D015221:Potassium Channels; D021122:Protein Subunits; D017470:Receptors, Glutamate; D014867:Water; D011188:Potassium