The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand

The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to provide adhesion between endothelial cells and leukocytes after injury or stress. ICAM-1 binds to leukocyte function-associated antigen (LFA-1) or macrophage-1 antigen (Mac-1). However, ICAM-1 is also used as a receptor by the major group of human rhinoviruses and is a catalyst for the subsequent viral uncoating during cell entry. The three-dimensional atomic structure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determined to 2.2-Å resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus–ICAM-1 complex. Rhinovirus attachment is confined to the BC, CD, DE, and FG loops of the amino-terminal Ig-like domain (D1) at the end distal to the cellular membrane. The loops are considerably different in structure to those of human ICAM-2 or murine ICAM-1, which do not bind rhinoviruses. There are extensive charge interactions between ICAM-1 and human rhinoviruses, which are mostly conserved in both major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is known to be mediated by a divalent cation bound to the insertion (I)-domain on the α chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs. Domain D1 has been docked with the known structure of the I-domain. The resultant model is consistent with mutational data and provides a structural framework for the adhesion between these molecules.

Primary structure and tissue distribution of two novel proline-rich γ-carboxyglutamic acid proteins

Two human cDNAs that encode novel vitamin K-dependent proteins have been cloned and sequenced. The predicted amino acid sequences suggest that both are single-pass transmembrane proteins with amino-terminal γ-carboxyglutamic acid-containing domains preceded by the typical propeptide sequences required for posttranslational γ-carboxylation of glutamic acid residues. The polypeptides, with deduced molecular masses of 23 and 17 kDa, are proline-rich within their putative cytoplasmic domains and contain several copies of the sequences PPXY and PXXP, motifs found in a variety of signaling and cytoskeletal proteins. Accordingly, these two proteins have been called proline-rich Gla proteins (PRGP1 and PRGP2). Unlike the γ-carboxyglutamic acid domain-containing proteins of the blood coagulation cascade, the two PRGPs are expressed in a variety of extrahepatic tissues, with PRGP1 and PRGP2 most abundantly expressed in the spinal cord and thyroid, respectively, among those tissues tested. Thus, these observations suggest a novel physiological role for these two new members of the vitamin K-dependent family of proteins.

Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide

Because ascorbic acid (AA) is concentrated in synaptic vesicles containing glutamic acid, we hypothesized that AA might act as a neurotransmitter. Because AA is an antioxidant, it might therefore inhibit nitric oxidergic (NOergic) activation of luteinizing hormone-releasing hormone (LH-RH) release from medial basal hypothalamic explants by chemically reducing NO. Cell membrane depolarization induced by increased potassium concentration [K+] increased medium concentrations of both AA and LH-RH. An inhibitor of NO synthase (NOS), NG-monomethyl-l-arginine (NMMA), prevented the increase in medium concentrations of AA and LH-RH induced by high [K+], suggesting that NO mediates release of both AA and LH-RH. Calcium-free medium blocked not only the increase in AA in the medium but also the release of LH-RH. Sodium nitroprusside, which releases NO, stimulated LH-RH release and decreased the concentration of AA in the incubation medium, presumably because the NO released oxidized AA to dehydro-AA. AA (10−5 to 10−3 M) had no effect on basal LH-RH release but completely blocked high [K+]- and nitroprusside-induced LH-RH release. N-Methyl-d-aspartic acid (NMDA), which mimics the action of the excitatory amino acid neurotransmitter glutamic acid, releases LH-RH by releasing NO. AA (10−5 to 10−3 M) inhibited the LH-RH-releasing action of NMDA. AA may be an inhibitory neurotransmitter that blocks NOergic stimulation of LH-RH release by chemically reducing the NO released by the NOergic neurons.

Effect of commercial amino acids on iron nutrition of tomato plants grown under lime-induced iron deficiency

The objective of this work was to study the effect of root and foliar application of two commercial products containing amino acids from plant and animal origin on iron (Fe) nutrition of tomato seedlings cultivated in two nutrient media: lime and normal nutrient solutions. In the foliar-application experiment, each product was sprayed with 0.5 and 0.7 mL L–1 2, 7, 12, and 17 d after transplanting. In the root application experiment, 0.1 and 0.2 mL L–1 of amino acids products were added to the nutrient solutions. In both experiments, untreated control plants were included as well. Foliar and root application of the product containing amino acids from animal origin caused severe plant-growth depression and nonpositive effects on Fe nutrition were found. In contrast, the application of the product from plant origin stimulated plant growth. Furthermore, significantly enhanced root and leaf FeIII-chelate reductase activity, chlorophyll concentration, leaf Fe concentration, and FeII : Fe ratio were found in tomato seedlings treated with the product from plant origin, especially when the amino acids were directly applied to the roots. These effects were more evident in plants developed under lime-induced Fe deficiency. The positive results on Fe uptake may be related to the action of glutamic acid, the most abundant amino acid in the formulation of the product from plant origin.

Organic properties of sediments and amino acids in iterstitial waters of ODP Holes 111-677A and 111-678B

The basement at Ocean Drilling Program (ODP) Sites 677 and 678 originated from the Galapagos spreading center of the Costa Rica Rift and has moved about 200 km over the last 6 m.y. (Fig. 1) (Shipboard Scientific Party, 1987, 1988; Scientific Drilling Party, 1987). Sediments about 300 m thick cover basement so young that basal sediments at Sites 677 and 678 have been reheated up to 60?-70?C at Site 677 and altered to limestone and/or chert (Shipboard Scientific Party, 1988). Sediments from both sites indicate (1) a high sedimentation rate (about 48 m/m.y.) and (2) biogenic silica and carbonate as the main constituents of sediments (Table 1) (Shipboard Scientific Party, 1988). Heatflow observations and measurements of interstitial water chemistry around the sites show that Site 677 is in a lower heatflow zone (166 mW/m**2; 1°12.14'N, 83°44.22'W) whereas Site 678 is located in a zone of higher heat flow (250 mW/m**2; 1°13.01'N, 83°43.39'W) (Langseth et al., 1988; Shipboard Scientific Party, 1988). In the flank hydrothermal systems, circulating solution is moving upward through the sedimentary column in zones of higher heat flow while it is moving downward in zones of lower heat flow (Anderson and Skilbeck, 1981). The chemistry of the interstitial waters is modified by several processes such as (1) diagenetic reactions and (2) advective and (3) diffusive transports of dissolved constituents. Analyses of Ca2+ and Mg2+ in interstitial waters from Sites 677 and 678 show that their profiles are mainly controlled by advective transport (Shipboard Scientific Party, 1988). In contrast, the interstitial-water profiles for NH4+, Si, and PO4[3-] are highly affected by reactions in the sediments. Site 677 offers a good opportunity to investigate amino acids in the interstitial waters because sediments of similar compositions have been deposited at constant rates of sedimentation. There are few previous works on amino acid distributions in interstitial waters (Henrichs and Parrington, 1979; Michaelis et al., 1982; Henrichs et al., 1984; Henrichs and Farrington, 1987; Ishizuka et al., 1988). In this chapter, we report (1) Rock-Eval analysis and (2) the composition of total hydrolyzable and dissolved free amino acids (THAA and DFAA, respectively) in the interstitial waters. Our objectives are to discuss (1) the possible origin of organic materials, (2) the characteristics of THAA and DFAA, and (3) their relationships in interstitial waters.