N-Terminal extracellular

These interactions involve adhesion proteins called selectins, which are found both on the rolling leukocytes and on the endothelial cells of the vascular walls. Selectins have a characteristic domain structure, consisting of an N-terminal extracellular lectin domain, a single epidermal growth factor (EGR) domain, a series of two to nine short consensus repeat (SCR) domains, a single transmembrane segment, and a short cytoplasmic domain. Lectin domains, first characterized in plants, bind carbohydrates... 

The structure of all TK receptors is similar in terms of expression oiTACR genes, since all these genes contain five exons intercalated by four introns [1, 5]. Exon I encodes for the N-terminal extracellular tail, the first intracellular (IC1) and extracellular (EC1) loops and the first, second, and third transmembrane domains (TM1, TM2, and TM3). Exon II encodes for the second intracellular (IC2) and extracellular (EC2) loops and the fourth transmembrane domain (TM4). Exon III encodes for the fifth transmembrane domain (TM5) and the third intracellular loop (IC3). Exon IV encodes for the sixth and seventh transmembrane domains (TM6 and TM7) and the third extracellular loop. Exon V encodes for the C-terminal intracellular tail only. A schematic drawing of the amino acid sequences and TK receptor organization is shown in Fig. 1. 

Gozansky E, Louis J, Caffrey M, Clore G. Mapping the binding of the N-terminal extracellular tail of the CXCR4 receptor to stromal cell-derived factor-1. J Mol Biol 2005 345 651-8. 

Pease JE, Wang J, Ponath PD, Murphy PM. The N-terminal extracellular segments of the chemokine receptors CCR1 and CCR3 are determinants for MIP-lalpha and... 

Structural and functional evidence clearly demonstrates that family C receptors function as dimers, either as homodimers or as heterodimers. The metabotropic glutamate receptors and the calcium sensors, as discussed in Section 2.6.1, are found as covalently connected dimers in which there is a disulfide bridge between a Cys residue located in a loop in the N-terminal extracellular domain of each monomer. This disulfide bridge apparently serves only to hold the monomers in close proximity, as the loop is so unstructured that it does not resolve in the x-ray structure. 

Figure 10.7 The EGF receptor. The N-terminal, extracellular region of the receptor contains 622 amino acids. It displays two cysteine-rich regions, between which the ligand-binding domain is located. A 23 amino acid hydrophobic domain spans the plasma membrane. The receptor cytoplasmic region contains some 542 amino acids. It displays a tyrosine kinase domain, which includes several tyrosine autophosphorylation sites, and an actin-binding domain that may facilitate interaction with the cell cytoskeleton...

Tones, M. A., Bendali, N., Flor, P. J., Knopfel, T., and Kuhn, R. (1995) The agonist selectivity of a class III metabotropic glutamate receptor, human mGluR4a, is determined by the N-terminal extracellular domain. NeuroReport 7,117-120. 

Abe, J., Suzuki, H Notoya, M Yamamoto, T., and Hirose, S. (1999) Ig-hepta, a novel member of the G protein-coupled hepta-helical receptor (GPCR) family that has immunoglobulin-like repeats in a long N-terminal extracellular domain and defines a new subfamily of GPCRs. J. Biol. Chem. 274,19957-19964. 

Tsouloufis, T., A. Mamalaki, M. Remoundos, and S.J. Tzartos (2000). Reconstitution of conformationally dependent epitopes on the N-terminal extracellular domain of the human muscle acetylcholine receptor alpha subunit expressed in Escherichia colt implications for myasthenia gravis therapeutic approaches. Int Immunol 12(9) 1255-1265. 

Three Trks have been identified, Trk A, B and C. Ligand-binding induces Trk receptor homodimerization. This activates the intrinsic cytoplasmic tyrosine kinase activity, resulting in receptor autophosphorylation and initiation of an intracellular response. A characteristic feature of the Trk family of receptors is the presence of a leucine-rich region near the N-terminal (extracellular) end of the molecule. 

LPH is a large (185 kDa) heptahelical receptor. It comprises three major domains (Figure 4a) (1) a long, glycosylated N-terminal extracellular domain (2) seven hydrophobic TMRs and (3) a long cytoplasmic tail. The ectodomain contains... 

Xia, H., von Zastrow, M., and Malenka, R. C. (2002). A novel anterograde trafficking signal present in the N-terminal extracellular domain of ionotropic glutamate receptors. / Biol. Chem. tTl, 47765-47769. 

Fig. 4. Schematic illustration of chemokine-receptor interactions. The transmembrane helices of the receptor, shown as blue tubes, were derived from the structure of rhodopsin (PDB code 1L9H). The chemokine (pink) and the N-terminal extracellular domain of the receptor were derived from the IL8-CXCR1 peptide complex shown in Fig. 5 (PDB code lILP). Except for the N-terminus, the loops of the receptor are not displayed. The figure illustrates the relative size of the receptor and ligand, and the interaction of the receptor N-terminus along one face of the chemokine. The interaction orients the N-terminal signal domain towards the receptor as displayed here it is oriented towards the helical bundle, which may or may not be correct for some chemokines. (See Color Insert.)...

Thordsen, I., Polzer, S., and Schreiber, M. (2002). Infection of cells expressing CXCR4 mutants lacking N-glycosylation at the N-terminal extracellular domain is enhanced for R5X4-dualtropic human immunodeficiency virus type-1. BMC Infect. Dis. 2, 31. 

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