Type 1 periplasmic binding fold superfamily; Type 1 periplasmic binding fold superfamily. This model and hierarchy represent the ligand binding domains of the LacI family of transcriptional regulators, periplasmic binding proteins of the ABC-type transport systems, the family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases including the family of natriuretic peptide receptors (NPRs), and the N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domains of the ionotropic glutamate receptors (iGluRs). In LacI-like transcriptional regulator and the bacterial periplasmic binding proteins, the ligands are monosaccharides, including lactose, ribose, fructose, xylose, arabinose, galactose/glucose and other sugars, with a few exceptions. Periplasmic sugar binding proteins are one of the components of ABC transporters and are involved in the active transport of water-soluble ligands. The LacI family of proteins consists of transcriptional regulators related to the lac repressor. In this case, the sugar binding domain binds a sugar which changes the DNA binding activity of the repressor domain. The periplasmic binding proteins are the primary receptors for chemotaxis and transport of many sugar based solutes. The core structures of periplasmic binding proteins are classified into two types, and they differ in number and order of beta strands: type 1 has six beta strands while type 2 has five beta strands per sub-domain. These two structural folds are thought to be distantly related via a common ancestor. Notably, while the N-terminal LIVBP-like domain of iGluRs belongs to the type 1 periplasmic-binding fold protein superfamily, the glutamate-binding domain of the iGluR is structurally similar to the type 2 periplasmic-binding fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74151447   1 MEVKSSVEKQGLNEEDYVNMFVEGFHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDF 80
Cdd:cd06386 282 MEVKSSVQKQGLNDEDYVNMFVEGFHDAILLYALALHEVLRNGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDF 361

                        90       100       110
                ....*....|....*....|....*....|
gi 74151447  81 SVVAMTDTEAGTQEVIGDYFGKEGRFQMRS 110
Cdd:cd06386 362 SVIAMTDVEAGTQEVIGDYFGKEGRFEMRP 391

ligand-binding domain of type C natriuretic peptide receptor; Ligand-binding domain of type C natriuretic peptide receptor (NPR-C). NPR-C is found in atrial, mesentery, placenta, lung, kidney, venous tissue, aortic smooth muscle, and aortic endothelial cells. The affinity of NPR-C for natriuretic peptides is ANP>CNP>BNP. The extracellular domain of NPR-C is about 30% identical to NPR-A and NPR-B. However, unlike the cyclase-linked receptors, it contains only 37 intracellular amino acids and no guanylyl cyclase activity. Major function of NPR-C is to clear natriuretic peptides from the circulation or extracellular surroundings through constitutive receptor-mediated internalization and degradation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74151447   1 MEVKSSVEKQGLNEEDYVNMFVEGFHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDF 80
Cdd:cd06386 282 MEVKSSVQKQGLNDEDYVNMFVEGFHDAILLYALALHEVLRNGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDF 361

                        90       100       110
                ....*....|....*....|....*....|
gi 74151447  81 SVVAMTDTEAGTQEVIGDYFGKEGRFQMRS 110
Cdd:cd06386 362 SVIAMTDVEAGTQEVIGDYFGKEGRFEMRP 391

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74151447  16 DYVNMFVEGFHDAILLYVLAlheVLRAGysKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDFSVV 83
Cdd:COG0683 239 REPSSYAAAGYDAALLLAEA---IEKAG--STDREAVRDALEGLKFDGVTGPITFDPDGQGVQPVYIV 301

ligand-binding domain of type C natriuretic peptide receptor; Ligand-binding domain of type C natriuretic peptide receptor (NPR-C). NPR-C is found in atrial, mesentery, placenta, lung, kidney, venous tissue, aortic smooth muscle, and aortic endothelial cells. The affinity of NPR-C for natriuretic peptides is ANP>CNP>BNP. The extracellular domain of NPR-C is about 30% identical to NPR-A and NPR-B. However, unlike the cyclase-linked receptors, it contains only 37 intracellular amino acids and no guanylyl cyclase activity. Major function of NPR-C is to clear natriuretic peptides from the circulation or extracellular surroundings through constitutive receptor-mediated internalization and degradation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74151447   1 MEVKSSVEKQGLNEEDYVNMFVEGFHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDF 80
Cdd:cd06386 282 MEVKSSVQKQGLNDEDYVNMFVEGFHDAILLYALALHEVLRNGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDF 361

                        90       100       110
                ....*....|....*....|....*....|
gi 74151447  81 SVVAMTDTEAGTQEVIGDYFGKEGRFQMRS 110
Cdd:cd06386 362 SVIAMTDVEAGTQEVIGDYFGKEGRFEMRP 391

ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of membrane guanylyl-cyclase receptors. Membrane guanylyl cyclases (GC) have a single membrane-spanning region and are activated by endogenous and exogenous peptides. This family can be divided into three major subfamilies: the natriuretic peptide receptors (NPRs), sensory organ-specific membrane GCs, and the enterotoxin/guanylin receptors. The binding of peptide ligands to the receptor results in the activation of the cytosolic catalytic domain. Three types of NPRs have been cloned from mammalian tissues: NPR-A/GC-A, NPR-B/ GC-B, and NPR-C. In addition, two of the GCs, GC-D and GC-G, appear to be pseudogenes in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are produced in the heart, and both bind to the NPR-A. NPR-C, also termed the clearance receptor, binds each of the natriuretic peptides and can alter circulating levels of these peptides. The ligand binding domain of the NPRs exhibits strong structural similarity to the type 1 periplasmic binding fold protein family.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74151447   1 MEVKSSVEKQGLN----EEDYVNMFVEGFHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDR 76
Cdd:cd06352 280 KEVKARAKEPPFYcydaSEEEVSPYAAALYDAVYLYALALNETLAEGGNYRNGTAIAQRMWNRTFQGITGPVTIDSNGDR 359

                        90       100       110
                ....*....|....*....|....*....|...
gi 74151447  77 YGDFSVVAMtDTEAGTQEVIGDYFGKEGRFQMR 109
Cdd:cd06352 360 DPDYALLDL-DPSTGKFVVVLTYDGTSNGLVVV 391

Ligand-binding domain of type A natriuretic peptide receptor; Ligand-binding domain of type A natriuretic peptide receptor (NPR-A). NPR-A is one of three known single membrane-spanning natriuretic peptide receptors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. In mammals there are three natriuretic peptides: ANP, BNP, and CNP. NPR-A is highly expressed in kidney, adrenal, terminal ileum, adipose, aortic, and lung tissues. The rank order of NPR-A activation by natriuretic peptides is ANP>BNP>>CNP. Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74151447   6 SVEKQGLNEED-YVNMFVEGFHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDFSVVA 84
Cdd:cd06385 298 AMEMFNFTVEDgLMNLIAASFHDGVLLYAHAVNETLAHGGTVTNGSAITQRMWNRSFYGVTGYVKIDENGDRETDFSLWD 377

                        90       100       110
                ....*....|....*....|....*....|..
gi 74151447  85 MTDtEAGTQEVIGDYFGKEGRFQMRSNVKYPW 116
Cdd:cd06385 378 MDP-ETGAFQIVSNYNGTSKELMAVPGRKIHW 408

Ligand-binding domain of membrane guanylyl cyclase G; This group includes the ligand-binding domain of membrane guanylyl cyclase G (GC-G) which is a sperm surface receptor and might function, similar to its sea urchin counterpart, in the early signaling event that regulates the Ca2+ influx/efflux and subsequent motility response in sperm. GC-G appears to be a pseudogene in human. Furthermore, in contrast to the other orphan receptor GCs, GC-G has a broad tissue distribution in rat, including lung, intestine, kidney, and skeletal muscle.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74151447  12 LNEEDYVNMFVEGFHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNR---TFEGIAGQVSIDANGDRYGDFSVVAM 85
Cdd:cd06372 291 ISSEDQVSPYSAYLHDAVLLYAMGLKEMLKDGKDPRDGRALLQTLRGYnqtTFYGITGLVYLDVQGERHMDYSVYDL 367

ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as natriuretic peptide receptors (NPRs), and N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of ionotropic glutamate rece; This CD represents the ligand-binding domain of the family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as the family of natriuretic peptide receptors (NPRs), and the N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the ionotropic glutamate receptors, all of which are structurally similar and related to the periplasmic-binding fold type 1 family. The family C GPCRs consists of metabotropic glutamate receptor (mGluR), a calcium-sensing receptor (CaSR), gamma-aminobutyric acid receptor (GABAbR), the promiscuous L-alpha-amino acid receptor GPR6A, families of taste and pheromone receptors, and orphan receptors. Truncated splicing variants of the orphan receptors are not included in this CD. The family C GPCRs are activated by endogenous agonists such as amino acids, ions, and sugar based molecules. Their amino terminal ligand-binding region is homologous to the bacterial leucine-isoleucine-valine binding protein (LIVBP) and a leucine binding protein (LBP). The ionotropic glutamate receptors (iGluRs) have an integral ion channel and are subdivided into three major groups based on their pharmacology and structural similarities: NMDA receptors, AMPA receptors, and kainate receptors. The family of membrane bound guanylyl cyclases is further divided into three subfamilies: the ANP receptor (GC-A)/C-type natriuretic peptide receptor (GC-B), the heat-stable enterotoxin receptor (GC-C)/sensory organ specific membrane GCs such as retinal receptors (GC-E, GC-F), and olfactory receptors (GC-D and GC-G).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74151447   4 KSSVEKQGLNEEDYVNMFVEGFHDAILLyvlalhevlragyskkdggkiiqqtwnrtfegiagqvsidangDRYGDFSVV 83
Cdd:cd06269 271 KSSKRKQGLNEEYELNNFAAFFYDAVLA-------------------------------------------DRPGQFSII 307

                        90       100
                ....*....|....*....|....*.
gi 74151447  84 AMTDTEAGTQEVIGDYFGkEGRFQMR 109
Cdd:cd06269 308 NLQYTEAGDYRKVGTWDS-EGGLNMS 332

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74151447  16 DYVNMFVEGFHDAILLYVLAlheVLRAGysKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDFSVV 83
Cdd:COG0683 239 REPSSYAAAGYDAALLLAEA---IEKAG--STDREAVRDALEGLKFDGVTGPITFDPDGQGVQPVYIV 301