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Query: UNIPROT:P06889 (Mol)
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Regulation in epidermal differentiation can best be studied if molecular mechanism can be associated with structural and functional changes. Such recognized associations include the cessation of mitosis through inhibition of DNA replication by a G1-inhibitor present in the suprabasal cells, the biosynthesis of a tonofilament-protein as an early event in keratinization, the biosynthesis of HRP0 (histidine-rich protein) and its polymerization to HRPI during the formation of keratohyalin, the conversion of HRPI to HRPII coincident with the loss of the nucleus from the granular cell, and the aggregation of the stratum corneum basic protein and keratin filaments to form fibers in the cornified cell. To this list can now be added changes in specificity for lectin-binding to the cell surface as the keratinocyte progresses toward the cutaneous surface. This report presents data on a) the conversion of HRPI to HRPII and b) the differential lectin-binding in the epidermis of the newborn rat. HRPI (Mol. Wgt. greater than or equal to 10(6)) and HRPII (Mol. Wgt. 6 X 10(4)) have similar unique amino acid compositions and exhibit extensive-but not complete-homology in primary structures as determined by peptide mapping after exposure to trypsin. When labeled by exposure in vivo to radioactivity histidine, about 75 of the labeled histidine from both HRPI and HRPII appeared in one peptide fraction in the map, HRPI appears to have on histidine-containing fragment which is not present in HRPII. This peptide appears to contain phosphate and to account for the organically-bound phosphate which was found in HRPI but not defected in HRPII. Changes which occur in the lectin-binding specificity of the cell during differentiation may result from either movement or chemical change in carbohydrates at the cell surface. Immunofluorescent studies have shown that an isolectin from Bandieraea simplicifolia with specificity for alpha-D-galactose binds to the surface of basal and lower spinous cells, a lectin from Ulex europaeus with specificity for alpha-L-focus labels spinous cells, and a second lectin from B. simplicifolia with specificity for N-acetyl-D-glucosamine labels cornified cells. The relationship fo these alterations in the carbohydrates of the cell surface in intracellular structural and/or functional changes in unknown.
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PMID:Molecular markers of differentiation in the epidermis of the newborn rat. 723 95

To explore potential inter-receptor interactions between Fc gamma RIIIB, a GPI-linked protein, and the leukocyte integrin CR3, we have prepared transfected 3T3 fibroblast cell lines expressing Fc gamma RIIIB, CR3, or both Fc gamma RIIIB and CR3. We test the hypothesis that Fc gamma RIIIB and CR3 are physically associated in membranes using fluorescence recovery after photobleaching (FRAP) and resonance energy transfer (r.e.t.) microscopy. Cells expressing Fc gamma RIIIB alone displayed a diffusion coefficient (D) of 3.4 x 10(-9) (+/- 2.9 x 10(-9) cm2/second and a mobile fraction (m.f.) of 0.73 (+/- 0.10). In contrast, Fc gamma RIIIB exhibited D = 2.5 x 10(-9) (+/- 1.4 x 10(-9) cm2/second (n.s.) and a m.f. of 0.48 (+/- 0.08) (p < 0.01) on cells expressing both Fc gamma RIIB and CR3, thus indicating that co-expression of CR3 constrains the lateral diffusion of Fc gamma RIIIB. To further test for a direct physical interaction between these gene products, (r.e.t.) microscopy was performed. Donor-labeled anti-CR3 and acceptor-labeled anti-Fc gamma RIIIB on cells expressing both receptors yielded a r.e.t. photon count rate of 8.9(+/- 6.4) kilocounts/second (kC/s), whereas CR3-to-CR3 measurements gave 1.6(+/- 0.6) kC/s (p < 0.01). Moreover, the addition of exogenous agents such as N-acetyl-D-glucosamine, but not indomethacin, diminished the magnitude of these interactions in transfectant membranes. These data support the notion that a subpopulation of Fc gamma RIIIB is physically associated with CR3 and that this association can be affected by exogeneous compounds.
J Mol Biol 1995 Apr 07
PMID:Interaction of Fc gamma receptor type IIIB with complement receptor type 3 in fibroblast transfectants: evidence from lateral diffusion and resonance energy transfer studies. 772 17

Biosignalling via lectins may involve modulation of protein kinase activities. This aspect of the biological action of mammalian and plant lectins has been investigated for their effect on the activity of the isolated epidermal growth factor receptor (EGFR). The constitutive tyrosine kinase activity of the epidermal growth factor receptor from rat liver, isolated by calmodulin-affinity chromatography, was activated by concanvalin A (ConA), and wheat germ agglutinin (WGA) to a similar extent as the measured enhancement induced by EGF. In contrast, two mannose-specific lectins, the mannan-binding protein (MBP) and serum amyloid P component (SAP), isolated from human serum, have inhibitory effects, both in the absence and presence of EGF. The differential effects of these lectins were tested using as phosphorylatable substrates a co-polymer of glutamic acid-tyrosine, as well as calmodulin. However, two galactoside-specific lectins, the laminin-binding beta-galactoside-binding 14 kDa lectin, isolated from bovine heart (14K-BHL), and the alpha/beta-galactoside-binding lectin, isolated from mistletoe (Viscum album L.) leaves (VAA), do not inhibit the EGFR tyrosine kinase activity. The sugar dependence of the lectin-mediated action was studied by inhibition assays. Mannose and a mannose-containing neoglycoprotein prevent the activating effect of ConA, and N-acetyl-D-glucosamine partially prevents the activation produced by WGA. However, mannose and mannose-containing neoglycoprotein were ineffective to reduce the inhibitory effect of MBP or SAP.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 Jan 26
PMID:Differential response of the epidermal growth factor receptor tyrosine kinase activity to several plant and mammalian lectins. 777 63

The crystal structure of a mutant hen egg white lysozyme, in which the key catalytic residue aspartic acid 52 has been changed to a serine residue (D52S HEWL), has been determined and refined to a crystallographic R value of 0.173 for all data F > 0 between 8 and 1.9 A resolution. The D52S HEWL structure is very similar to the native HEWL structure (r.m.s. deviation of main-chain atoms 0.20 A). Small shifts that result from the change in hydrogen bonding pattern on substitution of Asp by Ser were observed in the loop between beta-strands in the region of residues 46 to 49. D52S HEWL exhibits less than 1% activity against the bacterial cell wall substrate. Cocrystallisation experiments with the hexasaccharide substrate beta(1-4) polymer of N-acetyl-D-glucosamine (GlcNAc6) resulted in crystals between 5 days and 14 days after the initial mixing of enzyme and substrate. Analysis by laser absorption mass spectrometry of the oligosaccharides present after incubation with native and D52S HEWL under conditions similar to those used for crystal growth showed that after 14 days with native HEWL complete catalysis to GlcNAc3. GlcNAc2 and GlcNac had occurred but with D52S HEWL only partial catalysis to the major products GlcNAc4 and GlcNAc2 had occurred and at least 50% of the GlcNAc6 remained intact. X-ray analysis of the D52S-oligosaccharide complex crystals showed that they contained the product GlcNAc4. The structure of the D52S HEWL-GlcNAc4 complex has been determined and refined to an R value of 0.160 for data between 8 and 2 A resolution. GlcNAc4 occupies sites A to D in the active site cleft. Careful refinement and examination of 2Fo-Fc electron density maps showed that the sugar in site D has the sofa conformation, a conformation previously observed with the HEWL complex with tetra-N-acetylglucosamine lactone transition state analogue, the HEWL complex with the cell wall trisaccharide and the phage T4 lysozyme complex with a cell wall product. The semi-axial C(5)-C(6) geometry of the sofa is stabilised by hydrogen bonds from the O-6 hydroxyl group to the main-chain N of Val109 and main-chain O of Ala107. The sugar in site D adopts the alpha configuration, seemingly in conflict with the observation that the hydrolysis of beta (1-4) glycosidie linkage by HEWL proceeds with 99.9% retention of beta-configuration.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Biol 1994 Nov 11
PMID:Crystal structure of the mutant D52S hen egg white lysozyme with an oligosaccharide product. 796 6

The conformation in water of antimicrobial protein 2 from Amaranthus caudatus (Ac-AMP2) was determined using 1H NMR, DIANA and restrained molecular modeling. Ac-AMP2 is a 30 amino acid residue, lectin-like protein that specifically binds to chitin, a polymer of beta-1,4-N-acetyl-D-glucosamine. After sequence specific resonance assignments, a total of 198 distance restraints were collected from 2D NOESY buildup spectra at 500 MHz at pH 2, supplemented by a 2D NOESY spectrum at 600 MHz. The location of the three previously unassigned disulfide bridges was determined from preliminary DIANA structures, using a statistical analysis of intercystinyl distances. The solution structure of Ac-AMP2 is presented as a set of 26 DIANA structures, further refined by restrained molecular dynamics using a simulated annealing protocol in the AMBER force field, with a backbone r.m.s.d. for the well defined Glu3-Cys28 segment of 0.69(+/-0.12) angstroms. The main structural element is an antiparallel beta-sheet from Met13 to Lys23 including a betaI-turn over Gln17-Phel8 with a beta bulge at Gly19. In addition, a beta'I turn over Arg6-Gly7, a beta'III turn over Ser11-Gly12 and a helical turn from Gly24 to Cys28 are identified. This structure is very similar to the equivalent regions of the X-ray structure of wheat germ agglutinin and the NMR structure of hevein.
J Mol Biol 1996 May 03
PMID:H NMR study of the solution structure of Ac-AMP2, a sugar binding antimicrobial protein isolated from Amaranthus caudatus. 862 29

Sanfilippo B syndrome is caused by a deficiency of alpha-N-acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N-acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.
Hum Mol Genet 1996 Jun
PMID:Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B). 877 91

The role of cyclic AMP in the process of germ tube formation in Candida albicans was investigated. The exogenous supply of the nucleotide or of agents that raise its intracellular levels stimulated germination induced by N-acetyl-D-glucosamine; glucagon showed this same stimulatory effect on yeast cell transition to the hyphal form. Compounds, included glucagon, that stimulated hyphal formation, also notably enhanced the development of hyphae. The stimulatory effect of glucagon on germination was blocked by the specific antagonist des His1 [Glu9] glucagon amide, probably indicating an interaction of the hormone with a glucagon-like receptor on the membrane of the cells. Indirect immunofluorescence experiments showed that glucagon binds to the yeast cell surface. When N-acetyl-D-glucosamine was replaced by serum as inducing agent of germination, the stimulatory effect of glucagon was substantially augmented, the resulting of germination being more than 2.5-fold greater than that attained in the presence of N-acetyl-D-glucosamine; moreover, the glucagon concentration needed for half maximal stimulatory activity with serum as inducing agent was at least 50-fold lower than with N-acetyl-D-glucosamine. Monoclonal and polyclonal anti-glucagon antibodies blocked the effect of the hormone. An interesting result observed during these experiments was the fact that a definite period of incubation of C. albicans yeast cells with N-acetyl-D-glucosamine as inducer commits them to hyphal development. When serum was used as inducer, only yeast cells evaginated during the initial incubation period evolved to the hyphal form upon further incubation in the absence of serum.
Cell Mol Biol (Noisy-le-grand) 1996 Jun
PMID:Reassessment of the effect of glucagon and nucleotides on Candida albicans germ tube formation. 882 12

Rhizobia secrete specific lipo-chitooligosaccharide signals (LCOs) called Nod factors that are required for infection and nodulation of legumes. In Rhizobium sp. NGR234, the reducing N-acetyl-D-glucosamine of LCOs is substituted at C6 with 2-O-methyl-L-fucose which can be acetylated or sulphated. We identified a flavonoid-inducible locus on the symbiotic plasmid pNGR234a that contains a new nodulation gene, noeE, which is required for the sulphation of NGR234 Nod factors (NodNGR). noeE was identified by conjugation into the closely related Rhizobium fredii strain USDA257, which produces fucosylated but non-sulphated Nod factors (NodUSDA). R. fredii transconjugants producing sulphated LCOs acquire the capacity to nodulate Calopogonium caeruleum. Furthermore, mutation of noeE (NGRdelta noeE) abolishes the production of sulphated LCOs and prevents nodulation of Pachyrhizus tuberosus. The sulphotransferase activity linked to NoeE is specific for fucose. In contrast, the sulphotransferase NodH of Rhizobium meliloti seems to be less specific than NoeE, because its introduction into NGRdelta noeE leads to the production of a mixture of LCOs that are sulphated on C6 of the reducing terminus and sulphated on the 2-O-methylfucose residue. Together, these findings show that noeE is a host-specificity gene which probably encodes a fucose-specific sulphotransferase.
Mol Microbiol 1997 Jun
PMID:Sulphation of Rhizobium sp. NGR234 Nod factors is dependent on noeE, a new host-specificity gene. 921 62

Glycosidic residues of the mammalian zona pellucida (ZP) are known to be involved in sperm binding, suggesting the presence of complementary carbohydrate binding sites on spermatozoa. However, in previous studies, in which sperm suspensions were incubated with monosaccharides, no inhibitory effect was observed. Results of studies in which sperm were treated shortly after swim-up suggest that the use of non-capacitated cells may explain the apparently conflicting results. In the present report, we studied the effect of preincubation of capacitated spermatozoa with different monosaccharides on their ability to bind to ZP. After 5 h under capacitating conditions, spermatozoa were incubated in medium with or without a monosaccharide, resuspended in fresh medium and used for hemizona (HZ) binding assay. When ZH were incubated with spermatozoa treated with N-acetyl-D-glucosamine, D-mannose, D-fucose, L-fucose or D-galactose, a significant decrease in the number of spermatozoa bound was observed (level of inhibition: 62, 58, 82, 68 and 48% respectively) while treatment of spermatozoa with D-glucose produced no inhibition. Sugar treatment neither altered sperm motility nor the rate of acrosome reaction. These results suggest that N-acetylglucosamine, mannose, fucose and galactose residues are involved in human sperm-zona pellucida binding in vitro.
Mol Hum Reprod 1997 May
PMID:Glycosidic residues involved in human sperm-zona pellucida binding in vitro. 923 24

The utilization of various substrates by sperm from the cauda epididymidis of the tammar was examined because the major naturally occurring sugar in the semen of this species is N-acetyl-D-glucosamine (NAG) and not furctose, as in eutherian mammals. The sperm displayed a high level of endogenous respiration that supported motility for relatively prolonged periods of time in vitro. They also metabolised exogenous 14C-labelled glucose, NAG, sucrose, and acetate through glycolytic and/or oxidative processes to produce lactate and 14CO2 at varying rates. The rate of uptake of NAG by tammar sperm was about four times greater than that of other substrates. Glucose and/or NAG stimulated the rate of oxygen consumption by about 20%, but acetate stimulated oxygen consumption by more than 40%. The most striking findings were that NAG almost completely inhibited the oxidation of glucose and sucrose by the sperm and depressed the uptake of glucose, 3-O-methylglucose, and sucrose. Acetate oxidation also was inhibited by NAG, but only by about 50%. Tammar sperm generated substantial amounts of free glucose during incubation with NAG, but this and the inhibitory effects of NAG on glucose oxidation were not mimicked by rat sperm. It is proposed that tammar sperm fail to oxidise glucose in the presence of NAG because of the rapid cellular uptake of NAG relative to glucose. Also, the intracellular glucose and acetate liberated from NAG would compete with exogenous glucose for processing in the Embden-meyerhof and tricarboxylic acid (TCA) cycle pathways. It is also suggested that tammar sperm oxidise sucrose after extracellular hydrolysis into its glucose and fructose components. The biological implications of these metabolic and transport properties of tammar sperm have as yet to be determined.
Mol Reprod Dev 1998 Jan
PMID:The metabolic properties of spermatozoa from the epididymis of the tammar wallaby, Macropus eugenii. 940 99


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