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101.
The product of human herpesvirus 8 (HHV-8) open reading frame 74 (ORF74) is related structurally and functionally to cellular chemokine receptors. ORF74 activates several cellular signaling pathways in the absence of added ligands, and NIH 3T3 cells expressing ORF74 are tumorigenic in nude mice. We have generated a line of transgenic (Tg) mice with ORF74 driven by the simian virus 40 early promoter. A minority (approximately 30%) of the Tg mice, including the founder, developed tumors resembling Kaposi's sarcoma (KS) lesions, which occurred most typically on the tail or legs. The tumors were highly vascularized, had a spindle cell component, expressed VEGF-C mRNA, and contained a majority of CD31(+) cells. CD31 and VEGF-C are typically expressed in KS. Tumors generally (but not always) occurred at single sites and most were relatively indolent, although several mice developed large visceral tumors. ORF74 was expressed in a minority of cells in the Tg tumors and in a few other tissues of mice with tumors; mice without tumors did not express detectable ORF74 in any tissues tested. Cell lines established from tumors expressed ORF74 in a majority of cells, expressed VEGF-C mRNA, and were tumorigenic in nude mice. The resultant tumors grew rapidly, metastasized, and continued to express ORF74. Cell lines established from these secondary tumors also expressed ORF74 and were tumorigenic. These data strongly suggest that ORF74 plays a role in the pathology of KS and confirm and extend previous findings on the tumorigenic potential of ORF74. 相似文献
102.
The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P 总被引:2,自引:0,他引:2
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Tripp RA Dakhama A Jones LP Barskey A Gelfand EW Anderson LJ 《Journal of virology》2003,77(11):6580-6584
Respiratory syncytial virus (RSV) infection in the neonate can alter respiratory rates, i.e., lead to episodes of apnea. We show that RSV G glycoprotein reduces respiratory rates associated with the induction of substance P (SP) and G glycoprotein-CX3CR1 interaction, an effect that is inhibited by treatment with anti-G glycoprotein, anti-SP, or anti-CX3CR1 monoclonal antibodies. These data suggest new approaches for treating some aspects of RSV disease. 相似文献
103.
Spycher C Klonis N Spielmann T Kump E Steiger S Tilley L Beck HP 《The Journal of biological chemistry》2003,278(37):35373-35383
Using a stage-specific cDNA library from Plasmodium falciparum we have identified a gene coding for a novel histidine-rich protein (MAHRP-1). The gene is exclusively transcribed during early erythrocyte stages and codes for a small transmembrane protein. The C-terminal region contains a polymorphic stretch of histidine-rich repeats. Fluorescence microscopy studies using polyclonal mouse sera revealed that MAHRP-1 is located at the Maurer's clefts, which represent parasite-induced structures within the cytosol of infected erythrocytes. Biochemical studies showed that recombinant MAHRP-1 binds the toxic hemoglobin degradation product, ferriprotoporphyrin (FP) with a submicromolar dissociation constant and a stoichiometry determined by the number of DHGH motifs. The bound FP has increased peroxidase-like activity and is 10-fold more susceptible to H2O2-induced degradation compared with unbound FP. These properties of MAHRP-1 suggest it may play a protective role against oxidative stress, and its location at the Maurer's clefts suggests a function in promoting the correct trafficking of exported proteins, such as P. falciparum erythrocyte membrane protein-1. 相似文献
104.
Verrecchia F Tacheau C Wagner EF Mauviel A 《The Journal of biological chemistry》2003,278(3):1585-1593
105.
The effects of amino acid substitutions upon the behavior of poly(Leu)-rich alpha-helices inserted into model membrane vesicles were investigated. One or two consecutive Leu residues in the hydrophobic core of the helix were substituted with A, F, G, S, D, K, H, P, GG, SS, PG, PP, KK, or DD residues. A Trp placed at the center of the sequence allowed assessment of peptide behavior via fluorescence emission lambda(max) and dual quenching analysis of Trp depth [Caputo, G. A., and London, E. (2003) Biochemistry 42, 3265-3274]. In vesicles composed of dioleoylphosphatidylcholine (DOPC), all of the peptides with single substitutions adopted a transmembrane (TM) state. Experiments were also performed in thicker bilayers composed of dierucoylphosphatidylcholine (DEuPC). In DEuPC vesicles TM states were destabilized by mismatch between helix length and bilayer thickness. Nevertheless, in DEuPC vesicles TM states were still prevalent for peptides with single substitutions, although less so for peptides with P, K, H, or D substitutions. In contrast to single substitutions, certain consecutive double substitutions strongly interfered with formation of TM states. In both DOPC and DEuPC vesicles DD and KK substitutions abolished the normal TM state, but GG and SS substitutions had little effect. In even wider bilayers, a SS substitution reduced the formation of a TM state. A peptide with a PP substitution maintained the TM state in DOPC vesicles, but in DEuPC vesicles the level of formation of the TM state was significantly reduced. Upon disruption of normal TM insertion peptides moved close to the bilayer surface, with the exception of the KK-substituted peptide in DOPC vesicles, which formed a truncated TM segment. These studies begin to provide a detailed relationship between sequence and the stability of TM insertion and show that the influence of insertion-destabilizing residues upon hydrophobic helices can be strongly modulated by properties such as mismatch. For certain helix-forming hydrophobic sequences, sensitivity to lipid structure may be sufficient to induce large conformational changes in vivo. 相似文献
106.
107.
The effect of 2,4-dichlorophenol (DCP) was studied on the fully hydrated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)--water liposomes. The structure and the thermotropic phase behaviour of the liposomes was examined in the presence of DCP (DCP/DPPC molar ratio, varied from 2x10(-2) up to 1) using small- and wide-angle X-ray scattering (SAXS, WAXS) and freeze-fracture electron microscopy. The structural behaviour of the DPPC/DCP/water system was strongly dependent on the concentration of the DCP. In the pretransition range the DCP molecules (at 2x10(-2) DCP/DPPC molar ratio) induced the interdigitated phase beside the parent (gel and rippled gel) phases, locally which can be form at higher DCP concentration. When the DCP/DPPC molar ratio was increased the pretransition disappeared and the main transition was shifted to lower temperatures. In the molar ratio range from 2x10(-1) up to 5x10(-1), a coexistence of different phases was observed in the wide temperature range from 20 up to 40 degrees C. With a further increase of the DCP/DPPC molar ratio (6x10(-1) to 1) only the interdigitated gel phase occurred below 25 degrees C. A schematic phase diagram of DPPC/DCP/water system was constructed to summarise the results. 相似文献
108.
Terminal deletions of 1p36 result in a specific and common syndrome characterised by the following: growth delay, distinctive facial anomalies, hearing and visual deficits, heart defects, body asymmetry, moderate to severe psychomotor retardation, epilepsy, and self-abusive behaviour. The human gamma-aminobutyric acid A receptor delta-subunit gene (GABRD) encodes for one of at least 15 ligand-gated chloride channels for gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain. Recently we have mapped this gene by radiation hybrid mapping to the critical region of gene loss of the 1p36 deletion syndrome within 1p36.33. The complete complementary DNA (cDNA) sequence of GABRD was generated using assembled sequence of cDNA fragments already available, and 5'-rapid amplification of cDNA ends products. Fine physical mapping of the GABRD gene within this genomic interval was performed by screening bacterial artificial chromosome contigs spanning the critical region of the 1p36 deletion syndrome. The GABRD gene maps immediately proximal to the PRKCZ gene that is located between marker D1S243 and cosmid D1Z2--a region thought to be critical for cognition and speech development. The GABRD gene is expressed most abundantly in brain and has three alternative exons (1A-C) with alternative start codons at the 5'-end. Genomic localisation, function, and expression would suggest that the GABRD gene represents a good candidate for the neurodevelopmental and neuropsychiatric anomalies seen in the 1p36 deletion syndrome. 相似文献
109.
110.
Savita Dhanvantari Irina Arnaoutova Chris R Snell Peter J Steinbach Kelli Hammond Gregory A Caputo Erwin London Y Peng Loh 《Biochemistry》2002,41(1):52-60
Carboxypeptidase E (CPE) is a sorting receptor that directs the prohormone pro-opiomelanocortin (POMC) to the regulated secretory pathway, and is also a prohormone processing enzyme in neuro/endocrine cells. It has been suggested that the 25 C-terminal amino acids are necessary for the binding of CPE to secretory granule membranes, but its orientation in the membrane is not known. In this study, we examined the structure and orientation of the membrane-binding domain at the C-terminus of CPE. In vitro experiments using model membranes demonstrated that the last 22 amino acids of CPE (CP peptide) insert in a shallow orientation into lipid bilayers at low pH. Circular dichroism analysis indicated that the CP peptide adopts a partial alpha-helical configuration at low pH, and helix content increases when it is bound to lipid. Protease protection experiments, immunolabeling, and immunoisolation of intact secretory granules with a C-terminal antibody revealed a cytoplasmic domain in CPE, consistent with a transmembrane orientation of this protein. We conclude that the membrane-binding domain of CPE must adopt an alpha-helical configuration to bind to lipids, and that CPE may require another integral membrane "chaperone" protein to insert through the lipid bilayer in a transmembrane fashion. 相似文献