Type 2 periplasmic binding fold superfamily; This evolutionary model and hierarchy represent the ligand-binding domains found in solute binding proteins that serve as initial receptors in the transport, signal transduction and channel gating. The PBP2 proteins share the same architecture as periplasmic binding proteins type 1 (PBP1), but have a different topology. They are typically comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. The origin of PBP module can be traced across the distant phyla, including eukaryotes, archebacteria, and prokaryotes. The majority of PBP2 proteins are involved in the uptake of a variety of soluble substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the family includes ionotropic glutamate receptors and unorthodox sensor proteins involved in signal transduction. The substrate binding domain of the LysR transcriptional regulators and the oligopeptide-like transport systems also contain the type 2 periplasmic binding fold and thus they are significantly homologous to that of the PBP2; however, these two families are grouped into a separate hierarchy of the PBP2 superfamily due to the large number of protein sequences.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13729 205 CDTMKVGGNLDSKGYGIATPKGSALRNPVNLAVLKLNEQGLLDKLK 250

The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR1 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the AMPA receptor subunit GluR1, a member of non-NMDA (N-methyl-D-aspartate) type iGluRs which are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of AMPA receptors belongs to the periplasmic-binding fold type I. The AMPA receptors are the most commonly found receptor in the nervous system and sensitive to the artificial glutamate analog, AMPA. They consist of four types of subunits (GluR1, GluR2, GluR3, and GluR4) which combine to form a tetramer and play an important role in mediating the rapid excitatory synaptic current.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13729 205 CDTMKVGGNLDSKGYGIATPKGSALRNPVNLAVLKLNEQGLLDKLK 250

Ligand-gated ion channel; This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 6690044      1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:pfam00060 185 CDTMIVGETFATGGYGIATPKGSPLTDLLSLAILELEESGELDKLE 230

ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms];

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 6690044    6 VGGNLDSKGYGVATPKG-SALRNAVNLAVLKLNEQGLLDKL 45
Cdd:COG0834 173 VGEPLSGEPYGIAVRKGdPELLEAVNKALAALKADGTLDKI 213

The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR1 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the AMPA receptor subunit GluR1, a member of non-NMDA (N-methyl-D-aspartate) type iGluRs which are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of AMPA receptors belongs to the periplasmic-binding fold type I. The AMPA receptors are the most commonly found receptor in the nervous system and sensitive to the artificial glutamate analog, AMPA. They consist of four types of subunits (GluR1, GluR2, GluR3, and GluR4) which combine to form a tetramer and play an important role in mediating the rapid excitatory synaptic current.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13729 205 CDTMKVGGNLDSKGYGIATPKGSALRNPVNLAVLKLNEQGLLDKLK 250

The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the AMPA receptor subunit GluR4, a member of non-NMDA (N-methyl-D-aspartate) type iGluRs which are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of AMPA receptors belongs to the periplasmic-binding fold type I.The AMPA receptors are the most commonly found receptor in the nervous system and sensitive to the artificial glutamate analog, AMPA. They consist of four types of subunits (GluR1, GluR2, GluR3, and GluR4) which combine to form a tetramer and play an important role in mediating the rapid excitatory synaptic current.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13727 204 CDTMKVGGNLDSKGYGVATPKGSSLGNAVNLAVLKLNEQGLLDKLK 249

The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR2 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the AMPA receptor subunit GluR2, a member of non-NMDA (N-methyl-D-aspartate) type iGluRs which are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of AMPA receptors belongs to the periplasmic-binding fold type I. The AMPA receptors are the most commonly found receptor in the nervous system and sensitive to the artificial glutamate analog, AMPA. They consist of four types of subunits (GluR1, GluR2, GluR3, and GluR4) which combine to form a tetramer and play an important role in mediating the rapid excitatory synaptic current.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13726 204 CDTMKVGGNLDSKGYGIATPKGSSLGNAVNLAVLKLNEQGLLDKLK 249

The ligand-binding domain of non-NMDA (N-methyl-D-aspartate) type ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily; This subfamily represents the ligand-binding domain of non-NMDA (N-methyl-D-aspartate) type ionotropic glutamate receptors including AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) receptors (GluR1-4), kainate receptors (GluR5-7 and KA1/2), and orphan receptors delta 1/2. iGluRs form tetrameric ligand-gated ion channels, which are concentrated at postsynaptic sites in excitatory synapses where they fulfill a variety of different functions. While this ligand-binding domain of iGluRs is structurally homologous to the periplasmic binding fold type II superfamily, the N-terminal leucine/isoleucine/valine#binding protein (LIVBP)-like domain belongs to the periplasmic-binding fold type I.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13685 202 CDLTKVGEVFSEKGYGIAVQQGSPLRDELSLAILELQESGELEKLK 247

Ligand-gated ion channel; This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 6690044      1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:pfam00060 185 CDTMIVGETFATGGYGIATPKGSPLTDLLSLAILELEESGELDKLE 230

GluR6 subtype of kainate receptor, type 2 periplasmic-binding fold superfamily; This group contains glutamate receptor domain GluR. These domains are found in the GluR proteins that have been shown to function as L-glutamate activated potassium channels, also known ionotropic glutamate receptors or iGluRs. In addition to two ligand binding core domains, iGluRs typically have a channel-like domain inserted in the middle of the GluR-like domain. Animal iGluRs mediate the ion flux in the synapses of the CNS and can be subdivided into several classes depending on the neurotransmitter specificity and ion conductance properties. Their plant homologs have been shown to function in light signal transduction and calcium homeostasis. The GluR proteins belong to the PBPII superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13721 201 CNLTQIGGLIDSKGYGVGTPMGSPYRDKITIAILQLQEEGKLHMMK 246

The ligand-binding domain of the kainate subtype KA2 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily; This group contains the ligand-binding domain of the KA2 subunit of kainate receptor. While this ligand-binding domain is structurally homologous to the periplasmic binding fold type II superfamily, the N_terminal domain of kainate receptors belongs to the periplasmic-binding fold type I. There are five types of kainate receptors, GluR5, GluR6, GluR7, KA1, and KA2, which are structurally similar to AMPA and NMDA subunits of ionotropic glutamate receptors. KA1 and KA2 subunits can only form functional receptors with one of the GluR5-7 subunits. Moreover, GluR5-7 can also form functional homomeric receptor channels activated by kainate and glutamate when expressed in heterologous systems. Kainate receptors are involved in excitatory neurotransmission by activating postsynaptic receptors and in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism. Kainate receptors are closely related to AMAP receptors. In contrast of AMPA receptors, kainate receptors play only a minor role in signaling at synapses and their function is not well defined.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13725 200 CNLTQIGGLLDTKGYGIGMPLGSPFRDEITLAILQLQENNRLEILK 245

The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily; This group contains the ligand-binding domain of the KA1 subunit of kainate receptor. While this ligand-binding domain is structurally homologous to the periplasmic binding fold type II superfamily, the N_terminal domain of kainate receptors belongs to the periplasmic-binding fold type I. There are five types of kainate receptors, GluR5, GluR6, GluR7, KA1, and KA2, which are structurally similar to AMPA and NMDA subunits of ionotropic glutamate receptors. KA1 and KA2 subunits can only form functional receptors with one of the GluR5-7 subunits. Moreover, GluR5-7 can also form functional homomeric receptor channels activated by kainate and glutamate when expressed in heterologous systems. Kainate receptors are involved in excitatory neurotransmission by activating postsynaptic receptors and in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism. Kainate receptors are closely related to AMAP receptors. In contrast of AMPA receptors, kainate receptors play only a minor role in signaling at synapses and their function is not well defined.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13724 283 CNLTQIGGLLDTKGYGIGMPVGSVFRDEFDLAILQLQENNRLEILK 328

Glutamine binding domain of ABC-type transporter; the type 2 periplasmic binding protein fold; This periplasmic substrate-binding component serves as an initial receptor in the ABC transport of glutamine in bacteria and eukaryota. GlnH belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. PBP2 typically comprises of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 6690044    6 VGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKL 45
Cdd:cd00994 173 VGEPLTGEQYGIAFPKGSELREKVNAALKTLKADGTYDEI 212

The ligand-binding domain of putative ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains glutamate receptor domain GluR. These domains are found in the GluR proteins that have been shown to function as L-glutamate activated potassium channels, also known ionotropic glutamate receptors or iGluRs. In addition to two ligand binding core domains, iGluRs typically have a channel-like domain inserted in the middle of the GluR-like domain. Animal iGluRs mediate the ion flux in the synapses of the CNS and can be subdivided into several classes depending on the neurotransmitter specificity and ion conductance properties. Their plant homologs have been shown to function in light signal transduction and calcium homeostasis. The GluR proteins belong to the PBPII superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    1 CDTMKVGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13717 310 CDLQEVGEEFSRKPYAIAVQQGSPLKDELNYAILELQNDRFLEKLK 355

glutamine ABC transporter periplasmic protein; Reviewed

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 6690044     6 VGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQG 40
Cdd:PRK09495 198 VGDSLEAQQYGIAFPKGSELREKVNGALKTLKENG 232

Bacterial GluR0 ligand-binding domain; the type 2 periplasmic binding protein fold; Glutamate receptor domain GluR0. These domains are found in the GluR0 proteins that have been shown to function as prokaryotic L-glutamate activated potassium channels, also known ionotropic glutamate receptors or iGluRs. In addition to two ligand binding core domains, iGluRs typically have a channel-like domain inserted in the middle of the GluR-like domain. The GluR0 proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 6690044    6 VGGNLDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd00997 173 TGSVFLEENYGIVFPTGSPLRKPINQALLNLREDGTYDELY 213

The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the NR2 subunit of NMDA receptor family. The ionotropic N-methyl-d-asparate (NMDA) subtype of glutamate receptors serves critical functions in neuronal development, functioning, and degeneration in the mammalian central nervous system. The functional NMDA receptor is a heterotetramer composed of two NR1 and two NR2 (A, B, C, and D) or of NR3 (A and B) subunits. The receptor controls a cation channel that is highly permeable to monovalent ions and calcium and exhibits voltage-dependent inhibition by magnesium. Dual agonists, glutamate and glycine, are required for efficient activation of the NMDA receptor. Among NMDA receptor subtypes, the NR2B subunit containing receptors appear particularly important for pain perception; thus NR2B-selective antagonists may be useful in the treatment of chronic pain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 6690044    1 CDTMKVGGN--LDSKGYGVATPKGSALRNAVNLAVLKLNEQGLLDKLK 46
Cdd:cd13718 226 CKLVTIGSGkwFAMTGYGIALQKNSKWKRPFDLALLQFRGDGELERLE 273

ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms];

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 6690044    6 VGGNLDSKGYGVATPKG-SALRNAVNLAVLKLNEQGLLDKL 45
Cdd:COG0834 173 VGEPLSGEPYGIAVRKGdPELLEAVNKALAALKADGTLDKI 213

Substrate-binding domain of putative amino acid-binding protein; the type 2 periplasmic-binding protein fold; This putative amino acid-binding protein belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. PBP2 typically comprises of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 6690044    2 DTMKVGGNLDSKGY-GVATPKGSA-LRNAVNLAVLKLNEQGLLDKL 45
Cdd:cd13625 181 GVFALVGPVGGPTYfAWVIRKGDAeLRKAINDALLALKKSGKLAAL 226