RESUMO
Signal recognition particle (SRP) and SRP receptor are known to be essential components of the cellular machinery that targets nascent secretory proteins to the endoplasmic reticulum (ER) membrane. Here we report that the SRP receptor contains, in addition to the previously identified and sequenced 69-kD polypeptide (alpha-subunit, SR alpha), a 30-kD beta-subunit (SR beta). When SRP receptor was purified by SRP-Sepharose affinity chromatography, we observed the co-purification of two other ER membrane proteins. Both proteins are approximately 30 kD in size and are immunologically distinct from each other, as well as from SR alpha and SRP proteins. One of the 30-kD proteins (SR beta) forms a tight complex with SR alpha in detergent solution that is stable to high salt and can be immunoprecipitated with antibodies to either SR alpha or SR beta. Both subunits are present in the ER membrane in equimolar amounts and co-fractionate in constant stoichiometry when rough and smooth liver microsomes are separated on sucrose gradients. We therefore conclude that SR beta is an integral component of SRP receptor. The presence of SR beta was previously masked by proteolytic breakdown products of SR alpha observed by others and by the presence of another 30-kD ER membrane protein (mp30) which co-purifies with SR alpha. Mp30 binds to SRP-Sepharose directly and is present in the ER membrane in several-fold molar excess of SR alpha and SR beta. The affinity of mp30 for SRP suggests that it may serve a yet unknown function in protein translocation.
Assuntos
Peptídeos/isolamento & purificação , Receptores de Superfície Celular/análise , Receptores Citoplasmáticos e Nucleares , Receptores de Peptídeos , Animais , Fracionamento Celular , Cromatografia de Afinidade , Cães , Retículo Endoplasmático/análise , Microssomos Hepáticos/análise , RatosRESUMO
The signal recognition particle (SRP) and SRP receptor act sequentially to target nascent secretory proteins to the membrane of the ER. The SRP receptor consists of two subunits, SR alpha and SR beta, both tightly associated with the ER membrane. To examine the biogenesis of the SRP receptor we have developed a cell-free assay system that reconstitutes SR alpha membrane assembly and permits both anchoring and functional properties to be assayed independently. Our experiments reveal a mechanism involving at least two distinct steps, targeting to the ER and anchoring of the targeted molecule on the cytoplasmic face of the membrane. Both steps can be reconstituted in vitro to restore translocation activity to ER microsomes inactivated by alkylation with N-ethyl-maleimide. The characteristics elucidated for this pathway distinguish it from SRP-dependent targeting of secretory proteins, SRP-independent ER translocation of proteins such as prepromellitin, and direct insertion mechanisms of the type exemplified by cytochrome b5.
Assuntos
Retículo Endoplasmático/metabolismo , Microssomos/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Citoplasmáticos e Nucleares , Receptores de Peptídeos , Etilmaleimida/farmacologia , Lipossomos/metabolismo , Elastase Pancreática/metabolismo , Prolactina/metabolismo , Precursores de Proteínas/metabolismo , Receptores de Superfície Celular/biossíntese , Ribonucleoproteínas/metabolismo , Partícula de Reconhecimento de Sinal , Tripsina/metabolismoRESUMO
The signal recognition particle receptor (SR) is required for the cotranslational targeting of both secretory and membrane proteins to the endoplasmic reticulum (ER) membrane. During targeting, the SR interacts with the signal recognition particle (SRP) which is bound to the signal sequence of the nascent protein chain. This interaction catalyzes the GTP-dependent transfer of the nascent chain from SRP to the protein translocation apparatus in the ER membrane. The SR is a heterodimeric protein comprised of a 69-kD subunit (SR alpha) and a 30-kD subunit (SR beta) which are associated with the ER membrane in an unknown manner. SR alpha and the 54-kD subunits of SRP (SRP54) each contain related GTPase domains which are required for SR and SRP function. Molecular cloning and sequencing of a cDNA encoding SR beta revealed that SR beta is a transmembrane protein and, like SR alpha and SRP54, is a member of the GTPase superfamily. Although SR beta defines its own GTPase subfamily, it is distantly related to ARF and Sar1. Using UV cross-linking, we confirm that SR beta binds GTP specifically. Proteolytic digestion experiments show that SR alpha is required for the interaction of SRP with SR. SR alpha appears to be peripherally associated with the ER membrane, and we suggest that SR beta, as an integral membrane protein, mediates the membrane association of SR alpha. The discovery of its guanine nucleotide-binding domain, however, makes it likely that its role is more complex than that of a passive anchor for SR alpha. These findings suggest that a cascade of three directly interacting GTPases functions during protein targeting to the ER membrane.
Assuntos
Retículo Endoplasmático/enzimologia , GTP Fosfo-Hidrolases/metabolismo , Membranas Intracelulares/enzimologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Peptídeos/metabolismo , Partícula de Reconhecimento de Sinal/metabolismo , Sequência de Aminoácidos , Animais , Clonagem Molecular , Cães , Camundongos , Dados de Sequência Molecular , Ligação Proteica , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Peptídeos/genética , Homologia de Sequência de AminoácidosRESUMO
Membrane vesicles rich in nicotinic acetylcholine receptor prepared from Torpedo californica electric tissue have been irreversibly modified with quinacrine mustard, an alkylating derivative of the local anaesthetic quinacrine. The reaction blocked the ion channel regulated by the acetylcholine receptor. Acetylcholine still bound to the modified membrane vesicles with KD approx. 10(-8). The number of binding sites was reduced by up to 50%. Stopped-flow experiments showed that in contrast to what had been found with the reversibly binding quinacrine no fluorescence changes caused by energy transfer from the irradiated protein to the fluorescent local anaesthetic occurred after addition of agonist. This indicates that the conformational changes associated with the activation of the ion channel are blocked by the covalent reaction with quinacrine mustard. Analysis of the membrane vesicles by SDS-polyacrylamide gel electrophoresis showed that all polypeptide chains assumed to be part of the receptor complex had reacted with the mustard. Even small components, probably lipids, migrating with the dye front, showed fluorescence.
Assuntos
Órgão Elétrico/metabolismo , Mostarda de Quinacrina/farmacologia , Quinacrina/análogos & derivados , Receptores Colinérgicos/metabolismo , Animais , Transferência de Energia , Peixes , Membranas/metabolismo , Permeabilidade , Receptores Colinérgicos/efeitos dos fármacos , Sódio/metabolismo , Espectrometria de FluorescênciaRESUMO
Palytoxin, a toxin isolated from the Caribean corrall Palythoa caribaeorum, increases the cation permeability of excitable membranes in vitro. Three membrane systems have been investigated: axonal membranes from crayfish walking leg nerves, membranes rich in nicotinic acetylcholine receptor isolated from Torpedo californica electric tissue and, for control, artificial liposomes. Ion permeability of the latter was not affected by palytoxin, but with both biological membranes an increase in cation permeability was observed at a palytoxin concentration of 0.14 microM. Palytoxin-induced cation flow through the axonal membrane was not inhibited by tetrodotoxin, indicating that the voltage-dependent sodium channels were not involved. The effect of palytoxin on the receptor-rich membranes was not blocked by alpha-bungarotoxin, a competitive antagonist of the nicotinic acetylcholine receptor, nor by triphenylmethylphosphonium, a blocker of the receptor-ion channel. But with both the axonal and the receptor-rich membranes ouabain was an inhibitor of the palytoxin-induced cation flow. Evidence is presented that it is not the (Na+ + K+)-ATPase which is affected by palytoxin as has been postulated for similar observations with non-neuronal membranes (Chhatwal, G.S., Hessler, H.-J. and Habermann, E. (1983) Naunyn-Schmiedeberg's Arch. Pharmacol. 323, 261-268).
Assuntos
Acrilamidas , Permeabilidade da Membrana Celular/efeitos dos fármacos , Venenos de Cnidários/farmacologia , Animais , Astacoidea , Axônios/efeitos dos fármacos , Órgão Elétrico/efeitos dos fármacos , Técnicas In Vitro , Lipossomos , Lítio/metabolismo , Receptores Nicotínicos/efeitos dos fármacos , Sódio/metabolismo , TorpedoRESUMO
PD 151832 is a potent partial muscarinic agonist that displays a high level of functional selectivity for the muscarinic m1 receptor subtype, as evidenced by its selective stimulation of PI turnover and cellular metabolic activity in transfected Hm1-CHO cells at concentrations that produce minimal stimulation of other cloned human muscarinic receptors. PD 151832 enhanced the amplification of Hm1-transfected NIH-3T3 cells at concentrations lower than those required to produce similar effects in Hm2 or Hm3-transfected cells. The functional m1 selectivity of PD 151832 is consistent with its improvement of mouse water maze performance at doses far lower than those required to produce peripheral parasympathetic side effects.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Córtex Cerebral/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Oximas/farmacologia , Receptores Muscarínicos/metabolismo , Células 3T3/metabolismo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Células CHO , Córtex Cerebral/metabolismo , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Esvaziamento Gástrico/efeitos dos fármacos , Esvaziamento Gástrico/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Agonistas Muscarínicos/classificação , Agonistas Muscarínicos/metabolismo , Oximas/metabolismo , Fosfatidilinositóis/metabolismo , Ensaio Radioligante , Ratos , Receptor Muscarínico M1 , Relação Estrutura-Atividade , TransfecçãoRESUMO
The use of capillary culture chambers as artificial pancreas and artificial liver devices would be aided by an improved ability to control the movement of molecules through the capillary walls. The modeling and analysis of the flow and mass transfer in capillary cell culture chambers in which cultured mammalian cells are grown to form masses with tissue density in the extra-capillary spaces is desirable as a basis for scaleup and optimization of the particular microenvironment. The relative roles of diffusion and ultrafiltration with convection in enhancing mass transfer across the capillary membranes are poorly understood in real cell cultures and the effects on culture viability of flow conditions chosen to promote convective flow across the capillary membranes and through the cultured cell masses are also of interest. In this report, experience with materials and techniques for fabricating capillary culture chambers with a more readily analyzed fully defined regular geometric relationship between 90 to 100 capillaries in a parallel bundle is described. High and low pressure capillaries were interspersed in a regular array. Evidence is presented for retention of cell viability during flow conditions which were chosen to induce convective flow through the cultured cells in such a chamber.
Assuntos
Permeabilidade Capilar , Órgãos Artificiais , Sobrevivência Celular , Células Cultivadas , Meios de Cultura , Glucose/metabolismo , Humanos , Equilíbrio HidroeletrolíticoAssuntos
Acetilcolina/metabolismo , Ditioeritritol/farmacologia , Ditiotreitol/análogos & derivados , Mercaptoetanol/farmacologia , Receptores Colinérgicos/efeitos dos fármacos , Sódio/metabolismo , Animais , Sítios de Ligação , Carbacol/farmacologia , Sistema Livre de Células , Dissulfetos , Órgão Elétrico/metabolismo , Peixes , Ionóforos/metabolismo , Cinética , Proteínas de Membrana/metabolismo , Oxirredução , Ligação Proteica/efeitos dos fármacos , Receptores Colinérgicos/metabolismoAssuntos
Compostos de Anilina/farmacologia , Linfócitos B/imunologia , Hidroxibutiratos/farmacologia , Imunossupressores/farmacologia , Nitrilas/farmacologia , Linfócitos T/imunologia , Alcinos , Animais , Linfócitos B/efeitos dos fármacos , Gatos , Linhagem Celular , Células Cultivadas , Crotonatos , Cães , Humanos , Isoxazóis , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Primatas , Ratos , Ovinos , Especificidade da Espécie , Suínos , Linfócitos T/efeitos dos fármacos , ToluidinasAssuntos
Linfócitos B/efeitos dos fármacos , Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Nitrilas/farmacologia , Linfócitos T/efeitos dos fármacos , Alcinos , Animais , Formação de Anticorpos/efeitos dos fármacos , Linfócitos B/imunologia , Células Cultivadas , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Interleucina-4/farmacologia , Isoxazóis , Camundongos , Ratos , Baço , Linfócitos T/imunologiaAssuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos de Diferenciação de Linfócitos T/imunologia , Reação Enxerto-Hospedeiro , Receptores de Antígenos de Linfócitos T/imunologia , Transplante de Pele/imunologia , Animais , Complexo CD3 , Células Cultivadas , Glomerulonefrite/imunologia , Humanos , Terapia de Imunossupressão , Ativação Linfocitária , Substâncias Macromoleculares , Camundongos , Camundongos Endogâmicos , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos , Linfócitos T/imunologia , Timo/imunologiaRESUMO
The lipophilic cation triphenylmethylphosphonium (Ph3MeP+), which is widely used as a sensor for membrane potential with cells, organelles, and membrane vesicles, is shown also to accumulate in membranes rich in nicotinic acetylcholine receptor in a voltage-independent way. Evidence is presented that Ph3MeP+ in this system is bound to a cation-binding site of the ion channel that is part of the acetylcholine receptor complex. Binding is stimulated by cholinergic effectors (Kd = 13 microM in the absence of carbamoylcholine; Kd = 1.5 microM in the presence of 10 microM carbamoylcholine), and this stimulation is blocked by alpha-bungarotoxin. Ph3MeP+ blocks efflux of 22Na from receptor-rich microsacs and appears to compete with the channel ligand phencyclidine for a common binding site. In contrast to the binding of other proven channel ligands, Ph3MeP+-binding is not affected by desensitization.
Assuntos
Canais Iônicos/metabolismo , Oniocompostos , Receptores Colinérgicos/metabolismo , Receptores Nicotínicos/metabolismo , Compostos de Tritil/metabolismo , Transporte Biológico Ativo/efeitos dos fármacos , Técnicas In Vitro , Ligantes , Potenciais da Membrana , Sódio/metabolismo , Compostos de Tritil/farmacologiaRESUMO
This study was performed to evaluate the soluble interleukin-4 receptor (sIL-4R) as a potential antagonist of interleukin-4 (IL-4) in an infectious disease. It is shown that antigen-triggered proliferation and cytokine secretion of Leishmania major-specific, cloned Th2 cells in vitro can be inhibited dose dependently by recombinant murine, but not control human, sIL-4R. In vivo, we found that endogenous synthesis of IL-4 mRNA is upregulated during the first week of infection, while an increase of IL-4R mRNA occurred later after infection of BALB/c mice with L. major. To interfere successfully with the IL-4 ligand-receptor interaction, we therefore chose to treat infected BALB/c mice with recombinant sIL-4R during the onset (e.g., days 0 to 7) of the immune response. Treatment with murine, but not with human, sIL-4R during the first week of infection rendered BALB/c mice clinically resistant to L. major, led to a 7- to 12-fold reduction of the parasite load in spleen and lymph nodes at 7 weeks of infection, shifted the pattern of cytokines towards a Th1 type, and provided durable resistance against reinfection. Thus, it could be demonstrated that the balance among sIL-4R, membrane-bound IL-4R, and their ligand IL-4 can be modulated in vivo, thereby modifying the antiparasitic immune response. These results suggest a therapeutic value of sIL-4R in diseases in which neutralization of IL-4 is desirable.
Assuntos
Interleucina-4/antagonistas & inibidores , Leishmaniose Cutânea/imunologia , Receptores de Interleucina/fisiologia , Animais , Sequência de Bases , Feminino , Interleucina-4/análise , Interleucina-4/genética , Leishmaniose Cutânea/terapia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , RNA Mensageiro/análise , Receptores de Interleucina/análise , Receptores de Interleucina/genética , Receptores de Interleucina-4 , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêuticoRESUMO
To IL-1 beta is a principal mediator in the pathogenesis of inflammatory disease. The IL-1 beta-converting enzyme (ICE), a novel cysteine protease, is required for processing of the 31 kDa IL-1 beta precursor to generate the 17 kDa proinflammatory mature form. We investigated the effect of two irreversible peptidyl ICE inhibitors, VE-13,045 and VE-16,084, on IL-1 production in vitro and in vivo in acute and chronic inflammatory disease models. In vitro, VE-13,045 and VE-16084 inhibited IL-1 beta secretion by LPS-stimulated human adherent mononuclear cells (IC50's of 0.4 microM and 2.0 microM, respectively) and murine splenic monocytes (IC50's of 10 microM and 1.3 microM, respectively). Both VE-13,045 and VE-16,084 also inhibited LPS stimulated IL-1 alpha secretion, although with reduced potency. In vivo, a single intraperitoneal dose of VE-13,045 (50 mg/kg) administered to mice 60 to 75 minutes after a 40 mg/kg LPS challenge significantly reduced IL-1 beta serum levels by 50 to 70%. In the DBA/1J mouse model of Type II collagen-induced arthritis, prophylactic treatment with VE-13,045 (50 and 100 mg/kg/day) significantly delayed the onset of inflammation, with a 60% overall reduction in disease severity. VE-13,045 was more effective than either indomethacin (2 mg/kg/day) or methyl prednisolone (10 mg/kg/day). VE-13,045 was also effective in reducing inflammation and progression of arthritis when administered to mice with established disease. Histological analysis of wrist joints showed a reduction in synovial membrane damage, inflammatory cell infiltration and fibrosis, and cartilage erosion in VE-13,045-treated animals. This is the first demonstration of efficacy for an ICE inhibitor in a chronic disease model and suggests that ICE is an important target for design of anti-inflammatory or disease modifying drugs.
Assuntos
Artrite/tratamento farmacológico , Colágeno/toxicidade , Inibidores de Cisteína Proteinase/administração & dosagem , Interleucina-1/sangue , Oligopeptídeos/administração & dosagem , Animais , Artrite/induzido quimicamente , Artrite/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Humanos , CamundongosRESUMO
The B cell activation molecule CD40 and the p55 tumor necrosis factor receptor (p55TNFR) belong to the same family of structurally conserved proteins. We constructed a chimeric receptor consisting of the CD40 extracellular and transmembrane domains and the p55TNFR intracellular domain. This receptor hybrid retained the biological activity and the ligand specificity of the respective wild-type receptor domains. Thus it exerted a marked cytotoxic effect in three different transfected cell lines after activation not only with anti-CD40 antibody but also with CD40 ligand (CD40L) in soluble and membrane-bound forms. Using hybrid-transfected baby hamster kidney cells we demonstrated that herpesvirus saimiri-transformed human CD4+ T lymphocytes constitutively express bioactive CD40 ligand on their surface. The hybrid receptor-based assay was highly specific for CD40 activating reagents and more sensitive than an assay measuring CD40-mediated B cell rescue from apoptosis. Hence CD40/p55TNFR transfectants may be useful for dissecting CD40L-mediated events in T-B cell interactions, and also to detect a defective CD40L molecule in putative hyper-IgM syndrome patients.
Assuntos
Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos B/imunologia , Glicoproteínas de Membrana/biossíntese , Receptores do Fator de Necrose Tumoral/imunologia , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais , Antígenos CD/biossíntese , Antígenos de Diferenciação de Linfócitos B/biossíntese , Sequência de Bases , Antígenos CD40 , Ligante de CD40 , Linhagem Celular Transformada , Cricetinae , Testes Imunológicos de Citotoxicidade , Herpesvirus Saimiriíneo 2 , Humanos , Glicoproteínas de Membrana/imunologia , Camundongos , Dados de Sequência Molecular , Receptores de Interleucina/biossíntese , Receptores de Interleucina/imunologia , Receptores de Interleucina-4 , Receptores do Fator de Necrose Tumoral/biossíntese , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/imunologia , TransfecçãoRESUMO
Single-site glycomuteins of recombinant human erythropoietin (rhuEpo) were constructed and transiently and stably expressed in BHK-21 cells. The transient expression levels varied among muteins, being highest for mutein rhuEpoGln24 followed by wild-type rhuEpo (rhuEpowt). All other glycomuteins, including rhuEpoGln38, rhuEpoGln83, rhuEpoThr126, and rhuEpoGly126, were secreted at lower levels than rhuEpowt. Muteins expressed in stable cell lines showed similar differences in expression levels. Also each mutein could be affinity-purified from culture supernatants, and was biologically active in vivo. Based on secretion rates from BHK-21 cells, the most potent erythropoietin was rhuEpoGln24. This mutein is also considered to have biologic activities that are superior to rhuEpowt.
Assuntos
Eritropoetina/análogos & derivados , Eritropoetina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Animais , Sequência de Bases , Ligação Competitiva , Configuração de Carboidratos , Linhagem Celular , Cricetinae , Glicosilação , Humanos , Rim , Mesocricetus , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Processamento de Proteína Pós-Traducional , Receptores da Eritropoetina/metabolismo , Taxa Secretória , Relação Estrutura-AtividadeRESUMO
In this study, the effect of soluble IL-4 receptors (sIL-4R) on murine allergen-induced IgE and IgG1 production was examined. Lymphocytes from mice sensitized to the allergens ragweed (RW) or ovalbumin (OVA) in vivo were restimulated in vitro with the sensitizing allergen in the presence of either a soluble murine sIL-4R, a dimeric sIL-4R Ig fusion protein (sIL-4R/Fc), or anti-IL-4 antibody in 14-day cultures. Both monomeric and dimeric sIL-4R inhibited polyclonal IgE (approximately 70%) and IgG1 (approximately 35%) production in a dose-dependent fashion, similar to that observed in the presence of the anti-IL-4 antibody. Allergen-specific IgE and IgG1 were inhibited to a greater degree. Addition of sIL-4R was most effective when present in the culture during the first 3 days and added not later than day 6. In kinetic experiments, we distinguished ongoing IgE production from precommitted B cells versus newly induced IgE synthesis and found that newly induced IgE production was the major target of the sIL-4Rs. These data demonstrate the efficacy of sIL-4R in inhibiting the early stages of the IgE B-cell maturation pathway and indicate the potential of sIL-4R for the inhibition of IgE production in vivo.
Assuntos
Hipersensibilidade a Drogas/imunologia , Imunoglobulina E/biossíntese , Imunoglobulina G/biossíntese , Receptores de Interleucina/metabolismo , Animais , Anticorpos , Sequência de Bases , Células Cultivadas , DNA Complementar , Feminino , Linfonodos/imunologia , Camundongos , Dados de Sequência Molecular , Ovalbumina/farmacologia , Receptores de Interleucina/genética , Receptores de Interleucina/imunologia , Receptores de Interleucina-4 , Baço/imunologiaRESUMO
Recombinant soluble forms of transmembrane receptors can be produced in monomeric and dimeric versions. Binding affinity and neutralization potential of these different forms of soluble receptors depend on the quaternary structure of their ligands. Monomeric ligands will be bound with equal affinity by both forms, whereas trimeric ligands, e.g. members of the tumor necrosis factor family of ligands, interact with much higher affinity with dimeric soluble receptors than with monomeric ones.
Assuntos
Antígenos CD/química , Antígenos CD/metabolismo , Antígenos CD40/química , Antígenos CD40/metabolismo , Receptores de Interleucina-1/química , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina/química , Receptores de Interleucina/metabolismo , Sequência de Aminoácidos , Animais , Antígenos CD/biossíntese , Ligação Competitiva , Antígenos CD40/biossíntese , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/metabolismo , Interleucina-4/metabolismo , Cinética , Substâncias Macromoleculares , Camundongos , Modelos Estruturais , Dados de Sequência Molecular , Receptores de Interleucina/biossíntese , Receptores de Interleucina-1/biossíntese , Receptores de Interleucina-4 , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Sialoglicoproteínas/metabolismoRESUMO
The signal recognition particle (SRP) receptor is an integral membrane protein of the endoplasmic reticulum which, in conjunction with SRP, ensures the correct targeting of nascent secretory proteins to this membrane system. From the complementary DNA sequence we have deduced the complete primary structure of the SRP receptor and established that its amino-terminal region is anchored in the membrane. The anchor fragment and the cytoplasmic fragment contribute jointly to a functionally important region which is highly charged and may function in nucleic acid binding.