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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 496 REPPINTLQRLQA-AMIHDGyrlyVEKESSSLEMLENGTELFRQLYALMRQQVINDPQGFFiDSVEAGIKLIAEGGEDKA 574
Cdd:cd13685  112 KPTPIESLEDLAKqSKIEYG----TLKGSSTFTFFKNSKNPEYRRYEYTKIMSAMSPSVLV-ASAAEGVQRVRESNGGYA 186

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442628862 575 VLGGRETLFFNVQQYgSNNFQLSQKLYTRYSAVAVQIGCPFLGSLNNVLMQLFESGILDKMTA 637
Cdd:cd13685  187 FIGEATSIDYEVLRN-CDLTKVGEVFSEKGYGIAVQQGSPLRDELSLAILELQESGELEKLKE 248

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 496 REPPINTLQRLQA-AMIHDGyrlyVEKESSSLEMLENGTELFRQLYALMRQQVINDPQGFFiDSVEAGIKLIAEGGEDKA 574
Cdd:cd13685  112 KPTPIESLEDLAKqSKIEYG----TLKGSSTFTFFKNSKNPEYRRYEYTKIMSAMSPSVLV-ASAAEGVQRVRESNGGYA 186

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442628862 575 VLGGRETLFFNVQQYgSNNFQLSQKLYTRYSAVAVQIGCPFLGSLNNVLMQLFESGILDKMTA 637
Cdd:cd13685  187 FIGEATSIDYEVLRN-CDLTKVGEVFSEKGYGIAVQQGSPLRDELSLAILELQESGELEKLKE 248

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862  436 HQLFqKCIWFTLRLFLKQSCNELHNGYRAKFLTIVYWIAATYVLADvYSAQLTSQFARPAREPPINTLQRLQAamiHDGY 515
Cdd:pfam00060  41 FTLS-NSLWFSFGALVQQGHRENPRSLSGRIVVGVWWFFALILLSS-YTANLAAFLTVERMQSPIQSLEDLAK---QTKI 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862  516 RLYVEKESSSLEMLENGTELFRQlyaLMRQQVINDPQGFFIDSVEAGIKLIAEGGEDKAVLGGRETLF----FNVQQYGS 591
Cdd:pfam00060 116 EYGTVRGSSTYLFFRNSKIPSYK---RMWEYMESAKPSVKDALNEEGVALVRNGIYAYALLSENYYLFqrecCDTMIVGE 192

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862  592 NNFqlsqklyTRYSAVAVQIGCPFLGSLNNVLMQLFESGILDKMTAaeyakqyqeveatriykgsvQAKNSEAYSRTESY 671
Cdd:pfam00060 193 TFA-------TGGYGIATPKGSPLTDLLSLAILELEESGELDKLEK--------------------KWWPKSGECDSKSS 245

                         250       260
                  ....*....|....*....|...
gi 442628862  672 DSTViSPLNLRMLQGAFIALGVG 694
Cdd:pfam00060 246 ASSS-SQLGLKSFAGLFLILGIG 267

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 297 DSNDSFTGGIGLLQSGQADFFLGDVGLSWERRKAIEFS--FFTLADSGAFATHApRRLNEALAIMRPFKQDIWPHLILTI 374
Cdd:cd13724   63 EANGTWTGMVGELIARKADLAVAGLTITAEREKVIDFSkpFMTLGISILYRVHM-GRKPGYFSFLDPFSPGVWLFMLLAY 141

                         90
                 ....*....|....*...
gi 442628862 375 IFSGPIFYGIIAL-PYIW 391
Cdd:cd13724  142 LAVSCVLFLVARLtPYEW 159

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 496 REPPINTLQRLQA-AMIHDGyrlyVEKESSSLEMLENGTELFRQLYALMRQQVINDPQGFFiDSVEAGIKLIAEGGEDKA 574
Cdd:cd13685  112 KPTPIESLEDLAKqSKIEYG----TLKGSSTFTFFKNSKNPEYRRYEYTKIMSAMSPSVLV-ASAAEGVQRVRESNGGYA 186

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442628862 575 VLGGRETLFFNVQQYgSNNFQLSQKLYTRYSAVAVQIGCPFLGSLNNVLMQLFESGILDKMTA 637
Cdd:cd13685  187 FIGEATSIDYEVLRN-CDLTKVGEVFSEKGYGIAVQQGSPLRDELSLAILELQESGELEKLKE 248

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 216 RTFRVPVFHSPPW---------FWVTYCnnsfeedeefnsLDSIEKrkvrvtggrdhrllmlLSKHMNFRFKYIEAPGRT 286
Cdd:cd13717    2 RVYRIGTVESPPFvyrdrdgspIWEGYC------------IDLIEE----------------ISEILNFDYEIVEPEDGK 53

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 287 QGSMrsedgkDSNDSFTGGIGLLQSGQADFFLGDVGLSWERRKAIEFSFFTLADSG-AFATHAPRRLNEALAIMRPFKQD 365
Cdd:cd13717   54 FGTM------DENGEWNGLIGDLVRKEADIALAALSVMAEREEVVDFTVPYYDLVGiTILMKKPERPTSLFKFLTVLELE 127

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 366 IWPhliltiIFSgpifygiialpyiwrrrwansdvehlgelyihmtyLKEitprllklkprtvlsahqmphqlfqkCIWF 445
Cdd:cd13717  128 VWR------EFT-----------------------------------LKE--------------------------SLWF 140

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 446 TLRLFLKQSCNELHNGYRAKFLTIVYWIAATYVLAdVYSAQLTSQFARPAREPPINTLQRLQAAmihdgYRL-Y-VEKES 523
Cdd:cd13717  141 CLTSLTPQGGGEAPKNLSGRLLVATWWLFVFIIIA-SYTANLAAFLTVSRLQTPVESLDDLARQ-----YKIqYtVVKNS 214

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442628862 524 SSLEMLENGT---ELFRQLYALMRQQVINDPQGF-------------------------FIDSVEAGIKLIAEGGEDKAV 575
Cdd:cd13717  215 STHTYFERMKnaeDTLYEMWKDMSLNDSLSPVERaklavwdypvsekytkiyqamqeagLVANAEEGVKRVRESTSAGFA 294

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 442628862 576 LGGRETlffNVQQYGSNNFQLSQ---KLYTRYSAVAVQIGCPFLGSLNNVLMQLFESGILDKMTA 637
Cdd:cd13717  295 FIGDAT---DIKYEILTNCDLQEvgeEFSRKPYAIAVQQGSPLKDELNYAILELQNDRFLEKLKA 356

Kainate receptor of the 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        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442628862 265 LLMLLSKHMNFRFKYIEAPGRTQGSMrsedgKDSNDSFTGGIGLLQSGQADFFLGDVGLSWERRKAIEFS--FFTL 338
Cdd:cd13714   37 LLKELAKILGFNYTIRLVPDGKYGSY-----DPETGEWNGMVRELIDGRADLAVADLTITYERESVVDFTkpFMNL 107

The ligand-binding domain of ionotropic glutamate receptor family, a member of the periplasmic binding protein type II superfamily; This subfamily represents the ligand binding of ionotropic glutamate receptors. iGluRs are heterotetrameric ion channels that comprises of three functionally distinct subtypes based on their pharmacology and structural similarities: AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid), NMDA (N-methyl-D-aspartate), and kainate receptors. All three types of channels are also activated by the physiological neurotransmitter, glutamate. iGluRs are concentrated at postsynaptic sites, where they exert 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        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442628862 265 LLMLLSKHMNFRFKYIEAPGrtqgsmrSEDGKDSNDSFTGGIGLLQSGQADFFLGDVGLSWERRKAIEFS--FFTL 338
Cdd:cd00998   36 LLKELSQSLGFTYEYYLVPD-------GKFGAPVNGSWNGMVGEVVRGEADLAVGPITITSERSVVIDFTqpFMTS 104