Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A detailed analysis of further proteolytic degradation of fibrinogen fragment DH (Mr 95 kDa) was performed. Two new proteolytic fragments DLA and DL derived from DH-fragment have been purified and analyzed. The results obtained allow to propose a general scheme of DH-fragment proteolysis by stepwise splitting of their individual domains. The borders and molecular masses of these domains were evaluated on the base of proteolysis data.
Mol Biol (Mosk)
PMID:[A model of proteolysis of the fragment DH (95 kD) of the fibrinogen molecule]. 305 5

The protein composition of atheroma-free human thoracic intima was compared with that containing fatty streaks or fibro-fatty lesions utilizing two-dimensional gel electrophoresis (2-DE) and silver staining. Intimal proteins extracted with 9 M urea were separated by nonequilibrium pH gradient electrophoresis (NEPHGE) followed by polyacrylamide gel electrophoresis (PAGE) in the second dimension. NEPHGE-PAGE of proteins extracted from atheroma-free intima revealed several major proteins: actin, tropomyosin-like proteins, proteins with relative molecular weight (Mr) of 250,000 (P250), two proteins with Mr about 15,000 (P15a, P15b), and many medium proteins such as a myosin heavy chain, two myosin light chains, and proteins P47, P44, P32, P27, P20a, P20b, P19a, P19b. Several additional proteins were observed in intimas with fatty streaks and fibro-fatty lesions. Most of them, such as albumin, transferrin, Apo A-I, alpha 1-antitrypsin, fibrinogen beta-chain, IgG, appear to originate from plasma. Differences in protein composition of intima with fibro-fatty streaks compared with adjacent lesion-free intima varied from case to case and need further study. NEPHGE-PAGE in combination with isoelectric focusing (ISO)-PAGE revealed more intimal proteins in atheroma-free and diseased aortas than either method alone, proteins which might be quantitated, isolated for binding studies, and further evaluated for their potential role in atherogenesis.
Exp Mol Pathol 1986 Dec
PMID:Basic proteins in the human aortic intima: nonequilibrium two-dimensional electrophoretic analysis of tissue extracts. 309 75

In this study we have produced for the first time a native fibrinogen copolymer with a fragment of fibrin E. and the molecular mechanism of its formation was studied by different physicochemical methods. Based on the data of angular dependency of the Debay scattering factor, the average molecular mass, coefficients of translational diffusion and the intrinsic viscosity it was shown that the primary interaction comprised the "end-to-end" fibrinogen dimerization through the D-D contacts with the following fragment E specific binding. It resulted in the stable three-domain D-E-D knot formation. The structural flexibility of the copolymer determines the tendency to their folding and the strong intermolecular hydrodynamic interaction indicates the structural compactization. This correlates as we think, with the presence of the centers of lateral binding in the fibrinogen molecule. Single-strand copolymers aggregate when they reach their critical sweep length resulting in microgel formation with the raise of the molecular mass. We came to the conclusion that fibrinogen molecules are capable to associate due to the stable native conformation shift into the active state, thus demasking the reaction groups in the D-domain. Possible reasons for the lack of fibrinogen heteropolymer rigidity characteristic for the fibrin polymers are discussed.
Mol Biol (Mosk)
PMID:[Molecular organization of copolymers of fibrinogen-fibrin fragment]. 318 35

T-cell activation and induction of interleukin-2 (IL-2) expression in human T lymphocytes require both interaction of foreign antigen with the T-cell antigen receptor and protein kinase C (PKC) stimulation. Agents such as phorbol 12-myristate 13-acetate (PMA) that stimulate PKC augment the effects of antigen but are not sufficient for IL-2 activation. By analysis of deletion mutants, we identified three DNA sequences extending from -73 to -89, -217 to -255, and -263 to -279, designated IL-2 sites A, D, and E, respectively, that are required for maximal induction of IL-2 expression. One of these regions, site E, interacted with a protein (NF-IL-2E) present only in the nuclei of cells which have been stimulated. The other two sequences interacted with a protein (NF-IL-2A) that is constitutively expressed in T cells. When multiple tandem copies of either the E site or the A site were placed upstream of the gamma-fibrinogen promoter, they activated expression via this promoter in response to signals initiated at the antigen receptor but not following PMA stimulation. For this reason, we denoted them antigen receptor response elements. The uncoupling of antigen receptor and PKC requirements in these studies indicates that these signal pathways are, at least in part, distinct and integrated at the level of the gene.
Mol Cell Biol 1988 Apr
PMID:Characterization of antigen receptor response elements within the interleukin-2 enhancer. 326 3

The structural features of early fibrin oligomers produced during the initial stages of polymerization were investigated by rotatory shadowing after cryotechnical preparation. The building blocks of polymerization, namely fibrin monomer units (in analogy to fibrinogen itself), were found to exhibit a high degree of flexibility which is independent of fibrinopeptide A and B removal. Early polymers exhibited directed longitudinal growth and were frequently branched. Along the main oligomer axis, fibrin monomer units were randomly orientated. Within early oligomers, a given fibrin monomer unit was found to establish a single contact with each of its two neighbors, suggesting that during the early stages of polymerization, only one polymerization and one binding site are activated per fibrinogen molecule (becoming an AB2 fibrin monomer unit). This morphological feature was corroborated by the finding that early oligomer fractions are deficient in only 50% of releasable fibrinopeptide A. Early associations between AB2 fibrin monomer units were demonstrated to be reversible and to occur in the absence of direct domainal contact; interactions thus presumably occur via fine molecular protrusions on either D or E domains. The arrangement of AB2 fibrin monomer units within early oligomers suggests that, with respect to their structural organization, fibrinogen molecules are radially symmetrical through the E domain (implying an antiparallel organization of polymerization and binding sites). This pattern is inconsistent with a "top-bottom" model, and thus with "half-staggered double-stranded" polymer growth. The methodological problems responsible for the apparent conflict with previous morphological findings are discussed.
J Ultrastruct Mol Struct Res 1988 Jan
PMID:Molecular morphology of fibrin monomers and early oligomers during fibrin polymerization. 335 55

The morphology of equilibrium of soluble fibrin oligomers at different stages of assembly was studied. Results of Rauleigh's light scattering, analytical ultracentrifugation and viscosimetry show that fibrin-polymers throughout the entire homology range present rigid, rod-like structures dispersed by weight and dimensions. It was shown, that along with the traditional double-stranded chain protofibrills, where the monomer molecules are connected "end-to-center", there is an alternative variant, which is a result of single-stranded chain dimerization, where the monomers are formed up in an "end-to-end" fashion. Identity of physicochemical features of fibrin oligomers obtained by means of different enzyme activation of fibrinogen indicates that E1 and E2 sites interact with the complementary D1 and D2 sites only at the stage of protofibrill formation. It is suggested that the lateral aggregation is initiated by other sites that exist in fibrinogen and fibrin-monomer molecules in an accessible state. Thermodynamic reasons for the cooperative ability of protofibrill aggregation processes and gel-formation are discussed.
Mol Biol (Mosk)
PMID:[Structural transformations of fibrin oligomers]. 337 90

The use of derivatives of alpha-thrombin obtained by limited proteolysis, that have only a single peptide bond cleaved, allowed the unequivocal correlation between the change in covalent structure and alteration of the enzymatic properties. beta T-Thrombin contains a single cleavage in the surface loop corresponding to residues 65-83 of alpha-chymotrypsin [Birktoft, J. J., & Blow, D. M. (1972) J. Mol. Biol. 68, 187-240]. Compared with alpha-thrombin, this modification had a minor effect on the following: (1) The Michaelis constant (Km) for two tripeptidyl p-nitroanilide substrates increased 2-3 fold, whereas the catalytic constant (k cat) remained unaltered. (2) A 2-3 fold increase in the binding constant (KI) of a tripeptidyl chloromethane inhibitor was observed, but the inactivation rate constant (k i) was the same, which indicated that the nucleophilicity of the active-site histidyl residue had not changed. (3) The second-order rate constant for the inhibition by antithrombin III decreased 2-fold. Heparin accelerated the inactivation, and the degree of acceleration was similar to that obtained with alpha-thrombin. Pronounced effects of the cleavage of this loop were found. (1) The cleavage of fibrinogen was approximately 80-fold slower than that with alpha-thrombin. This was mainly due to a 40-fold decrease in k cat. In contrast, only a 1.9-fold increase in the Michaelis constant was observed. (2) The affinity for thrombomodulin had decreased 39-fold compared to alpha-thrombin. epsilon-Thrombin contains a single cleaved peptide bond in the loop corresponding to residues 146-150 in alpha-chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzymatic properties of proteolytic derivatives of human alpha-thrombin. 337 50

Human fibrinogen was observed by electron microscopy following rotary shadowing with tungsten. Structure analysis of the molecules was performed by image processing of electron micrographs. A method is described for selection, alignment, and classification of molecules. The widely accepted overall trinodular structure of the protein was observed. The flexibility about the central domain of the molecule was quantitatively analyzed. A Gaussian distribution of this conformational parameter was obtained having an average corresponding to a maximally extended structure. Correspondence analysis applied to the aligned images showed that the degree of folding of the molecule was continuously distributed. The averaged structure of fibrinogen was estimated to be 450 A long. The central domain had a diameter of 50 A and the peripheral domains were 90 A long and 50 A wide. The latter regions had two separated maxima of scattering density.
J Ultrastruct Mol Struct Res 1988 Mar
PMID:Structure analysis of fibrinogen by electron microscopy and image processing. 340 3

When spread as a monolayer on the surface of hydrophobic beads and injected into mice, the mycobacterial glycolipid, trehalose 6,6'-dimycolate, reproduces the biologic effects traditionally associated with virulent mycobacteria, including acute inflammation, granuloma formation, and immune adjuvancy. Repeated intraperitoneal injection of glycolipid-coated beads into young C57Bl/6 mice elicits a granulomatous peritonitis, with concomitant dissemination of beads from the peritoneum to distant organs. Glycolipid-coated beads which disseminate from the peritoneum to other sites elicit neither acute inflammation nor granulomata. The coagulation system may be involved in the dissemination of glycolipid-coated beads as evidenced by the following: fibrinogen is a necessary cofactor of the trehalose dimycolate monolayer; diffuse peritoneal and pulmonary hemorrhage accompanies bead dissemination; peritoneal exudate collected shortly after intraperitoneal injection of glycolipid-coated beads is enriched in coagulant activity; coagulability of blood from trehalose dimycolate-treated animals is reduced; and anticoagulation inhibits the inflammatory response to glycolipid-coated beads. In this report, the dissemination of trehalose dimycolate-coated beads is characterized, and a role for the coagulation system in this process is proposed.
Exp Mol Pathol 1987 Apr
PMID:Dissemination of beads coated with trehalose 6,6'-dimycolate: a possible role for coagulation in the dissemination process. 355 32

Interactions between fibrin and arterial endothelial cells of rat iliac arteries in vivo were studies electron microscopically using a newly devised method. The microvilli became attached to the fibrin threads in an initial period of fibrinolysis. These threads had a fine granular appearance in the lysed areas. Fibrinolytically active endothelial cells had an active vesicular transport for ferritin particles injected concomitantly with the fibrinogen-thrombin mixture, thereby implying the enhancement of endothelial permeability in the lysed areas. However, fibrinolytically inactive endothelial cells coexisted in the same arteries. The denuded intima showed no lytic changes in the fibrin threads. These results indicate that the microvilli of the endothelial cells may plan an important role in the releasing plasminogen tissue activator from the endothelial cells and that there is a heterogeneity with regard to reactivity of each endothelial cell to fibrin.
Exp Mol Pathol 1986 Jun
PMID:Pathophysiological effects of fibrin on arterial endothelial cells in vivo: an electron microscopic study. 372 Sep 24


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