Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The domain organization of the zymogen subunits of the first component of human complement C1s, C1r2 and the complex C1s-C1r2-C1s was studied by electron microscopy. In the absence of Ca2+, monomeric C1s was visualized as a dumb-bell-shaped molecule consisting of two globular domains (center-to-center distance 11 nm) connected by a rod. One of the globular domains is assigned to the light chain (B-chain) of the activated molecule, which is homologous to trypsin and other serine proteases. The second globular domain and the rod are assigned to the heavy chain (A-chain) of CIs. The subunit C1r is a stable dimer in the presence or absence of Ca2+. This dimer C1r2 was visualized as composed of two dumb-bells of dimensions similar to those observed for C1s. These are connected near the junctions between the rod and one of the globular domains. This leads to the structure of an asymmetrical X with two inner closely spaced globules (center-to-center distance 7 nm) and two outer globules at a larger distance (14 nm). By comparison with fragment C1rII2, in which part of the A-chain is removed, the inner globular domains were assigned to the catalytic B-chains. This characteristic structure of C1r2 is readily recognized in the central portion of the thread-like 54 nm long C1s-C1r2-C1s complex formed in the presence of Ca2+. By affinity-labeling of C1s with biotin and visualization of avidin-ferritin conjugates in the reconstituted complex, it was demonstrated that C1s forms the outer portion of the complex. A detailed model of C1s-C1r2-C1s is proposed, according to which two C1s monomers bind to the outer globes of C1r2 by contacts between their heavy chains and those of C1r. According to this model the catalytic domains of C1r are located in the center and those of C1s at the very tips of the C1s-C1r2-C1s complex. On the basis of the structure of C1s-C1r2-C1s, we derived a detailed model of the C1 complex (composed of C1q and the tetrameric complex) and we discuss this model with a view to finding a possible activation mechanism of C1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional model of subcomponent C1 of human complement. 302 30

The preparation, properties, and some applications of ferritin conjugates of two plant agglutinins, concanavalin A and Ricinus communis agglutinin, are reported. These conjugates serve as specific electron-dense stains for cell- and membrane-bound saccharide residues of the alpha-D-mannopyranosyl and beta-D-galactopyranosyl configurations, respectively, and as examples of a wide range of ferritin-plant agglutinin conjugates useful as high resolution saccharide stains. By using a technique for preparing flattened membrane specimens, it was found with a variety of mammalian cell plasma membranes (lymphocyte, lymphoma, and myeloma and normal, spontaneously and virally transformed fibroblasts) that the ferritin conjugates were localized exclusively to the exterior face of the membrane, with essentially none found on the cytoplasmic face. On the exterior face the topographical distribution of ferritin conjugates appeared to be random. The asymmetrical distribution of saccharide residues to the outer membrane face can be explained by an "assembly line" process whereby new plasma membrane is made from intracellular precursor membranes. It also suggests that the saccharide-containing components of the plasma membrane do not rotate at any appreciable rate from one membrane surface to the other.
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PMID:The distribution and asymmetry of mammalian cell surface saccharides utilizing ferritin-conjugated plant agglutinins as specific saccharide stains. 412 77

Rhodopseudomonas viridis thylakoid membrane polypeptides were characterised by SDS gels, 2 D gels and surface-specific iodination. Four polypeptides with apparent molecular weights of 38 000, 33 000, 27 000, and 24 000 (reaction centre) and three low molecular weight polypeptides 11 000, 8000 and 6000 (probably light harvesting polypeptides) were identified. Antibodies were produced against the polypeptides eluted from SDS gels and tested for specificity by an immunoblotting assay. The antibodies were bound to the membranes and viewed by electron microscopy using a modification of the ferritin labelling technique. It is suggested that antigenic determinants for the 38 000, 33 000, and 27 000 reaction centre polypeptides and the 11 000 and 8000 low molecular weight polypeptides are present on the cytoplasmic membrane surface. The 33 000, 27 000, 11 000 and 6000 polypeptides appear to have surface-located residues which can be iodinated. The photosynthetic membrane of Rps. viridis appears to be a highly asymmetrical membrane.
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PMID:Localisation of Rhodopseudomonas viridis reaction centre and light harvesting proteins using ferritin-antibody labelling. 618 15

The in vitro incorporation of cytochrome b5 into purified plasma membranes was investigated by biochemical and immunological methods. Plasma membrane preparations incorporated three times less cytochrome b5 than did microsomal preparations; 60% of this cytochrome b5 could not be reduced by the NADH-cytochrome b5 reductase and considered as being bound to the plasma membrane. The morphological observations made after the immunochemical labeling of cytochrome b5 clearly showed a good but asymmetrical distribution of the ferritin labeling: only the inner face of the plasma membrane incorporated cytochrome b5. These results are discussed with respect to theories which concern the subcellular membrane relationships in the cell.
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PMID:The binding of cytochrome b5 to plasma membranes of rat liver: its implication for membrane specificity and biogenesis. 737 3

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.
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PMID:Klinefelter's syndrome presenting with leg ulcers. 1536 65