Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Origin Recognition Complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed2005

Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor.

Natural killer T cells express a conserved, semi-invariant alphabeta T cell receptor that has specificity for self glycosphingolipids and microbial cell wall alpha-glycuronosylceramide antigens presented by CD1d molecules. Here we report the crystal structure of CD1d in complex with a short-chain synthetic variant of alpha-galactosylceramide at a resolution of 2.2 A. This structure elucidates the basis for the high specificity of these microbial ligands and explains the restriction of the alpha-linkage as a unique pathogen-specific pattern-recognition motif. Comparison of the binding of altered lipid ligands to CD1d and T cell receptors suggested that the differential T helper type 1-like and T helper type 2-like properties of natural killer T cells may originate largely from differences in their 'loading' in different cell types and hence in their tissue distribution in vivo.

Amino Acid Motifs↗
PubMed1994

Reaction mechanism underlying CMP-N-acetylneuraminic acid hydroxylation in mouse liver: formation of a ternary complex of cytochrome b5, CMP-N-acetylneuraminic acid, and a hydroxylation enzyme.

We have proposed that CMP-N-acetylneuraminic acid (CMP-NeuAc) hydroxylation is mediated by an electron transport system consisting of cytochrome b5 (b5), b5 reducing factor(s), and CMP-NeuAc hydroxylase, all of which have been detected in the cytosolic fraction of mouse liver [Kozutsumi, Y., Kawano, T., Yamakawa, T., & Suzuki, A. (1990) J. Biochem. 108, 704-706]. In order to elucidate the reaction mechanism underlying CMP-NeuAc hydroxylation, the interaction between b5 and the hydroxylase was studied using a b5-immobilized affinity column. The enzyme activity was retarded on the b5 column in the presence of the substrate, CMP-NeuAc, but not in the presence of the reaction product, CMP-N-glycolyneuraminic acid (CMP-NeuGc). These findings suggest that the binding of CMP-NeuAc to CMP-NeuAc hydroxylase changes the conformation of the enzyme so as to construct a recognition site for b5, followed by the formation of a ternary complex through this domain. Then the transport of electrons from NAD(P)H to the enzyme through b5 takes place, CMP-NeuAc is converted to CMP-NeuGc, and finally the ternary complex dissociates into its components to release CMP-NeuGc. It is known that a soluble form of b5 is abundant in erythrocytes and is synthesized from a mRNA different from that for the microsomal form of b5. In order to determine the origin of b5 detected in the cytosolic fraction of mouse liver, the molecular forms of b5 mRNA expressed in mouse liver were analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Complex regional pain syndrome I in the upper extremity.

Complex regional pain syndrome (CRPS) I, formerly known as reflex sympathetic dystrophy (RSD), is a painful neuropathic condition that most commonly affects a traumatized extremity. It is characterized by pain that is out of proportion to the original injury, has a distal predominance, and is not attributable to a specific peripheral nerve injury. The name RSD has been changed to CRPS I reflecting the fact that although sympathetic dysfunction can maintain the painful state, it is not the essential pathophysiologic lesion. Successful treatment hinges on early recognition of suspected cases, prompt referral to pain specialists, and ultimately pain control and return of limb function. Treatments range from noninvasive medications and therapies to sympathetic ganglion blockade and sympathectomy. The sports medicine physician is in an ideal position to recognize CRPS I in its earliest stages postinjury, and is advised to make prompt referral to a pain specialist when suspected.

Diagnosis, Differential↗
PubMed1998

Recruitment and loading of the E1 initiator protein: an ATP-dependent process catalysed by a transcription factor.

Initiation of DNA replication critically depends on ori recognition as well as on catalytic activities of the initiator complex. For replication of papillomaviruses the catalytic activities for initiation are provided by the E1 protein. Here, we show that the transcription factor E2 acts to assemble E1 into a complex active for ori distortion in two steps. First, cooperative DNA binding of E1 and E2 generates a sequence-specific ori recognition complex. In the second ATP-dependent step, E2 is displaced and additional E1 molecules are incorporated. The net result is a final complex with low sequence specificity deposited onto a specific sequence in the DNA. This may be a general strategy to accomplish specific positioning of protein complexes with low sequence specificity.

Adenosine Triphosphate↗
PubMed2000

Recognition of multiple drugs by a single protein: a trivial solution of an old paradox.

Multidrug-efflux transporters recognize scores of structurally dissimilar toxic compounds and expel them from cells. The broad chemical specificity of these transporters challenges some of the basic dogmas of biochemistry and remains unexplained. To understand, at least in principle, how a protein can recognize multiple compounds, we analysed the transcriptional regulator of the Bacillus subtilis multidrug transporter Bmr. This regulator, BmrR, binds multiple dissimilar hydrophobic cations and, by activating the expression of the Bmr transporter, causes their expulsion from the cell. Crystallographic analysis of the complexes of the inducer-binding domain of BmrR with some of its inducers revealed that ligands cause disordering of the surface alpha-helix and penetrate the hydrophobic core of the protein, where they form multiple van der Waals and stacking interactions with hydrophobic amino acids and an electrostatic bond with the buried glutamic residue. Mutational analysis of the binding site suggests that each ligand forms a unique set of atomic contacts with the protein: each tested mutation exerted disparate effects on the binding of different ligands. The example of BmrR demonstrates that a protein can bind multiple compounds with micromolar affinities by using only electrostatic and hydrophobic interactions. Its ligand specificity can be broadened by the flexibility of the binding site. It therefore seems that the commonly expressed fascination with the broad specificity of multidrug transporters is misdirected and originates from an almost exclusive familiarity with the more sophisticated processes of specific molecular recognition that predominate among existing proteins.

Bacterial Proteins↗
PubMed1999

Crystal structure of chondroitinase B from Flavobacterium heparinum and its complex with a disaccharide product at 1.7 A resolution.

Glycosaminoglycans (GAGs) are a family of acidic heteropolysaccharides, including such molecules as chondroitin sulfate, dermatan sulfate, heparin and keratan sulfate. Cleavage of the O-glycosidic bond within GAGs can be accomplished by hydrolases as well as lyases, yielding disaccharide and oligosaccharide products. We have determined the crystal structure of chondroitinase B, a glycosaminoglycan lyase from Flavobacterium heparinum, as well as its complex with a dermatan sulfate disaccharide product, both at 1.7 A resolution. Chondroitinase B adopts the right-handed parallel beta-helix fold, found originally in pectate lyase and subsequently in several polysaccharide lyases and hydrolases. Sequence homology between chondroitinase B and a mannuronate lyase from Pseudomonas sp. suggests this protein also adopts the beta-helix fold. Binding of the disaccharide product occurs within a positively charged cleft formed by loops extending from the surface of the beta-helix. Amino acid residues responsible for recognition of the disaccharide, as well as potential catalytic residues, have been identified. Two arginine residues, Arg318 and Arg364, are found to interact with the sulfate group attached to O-4 of N-acetylgalactosamine. Cleavage of dermatan sulfate likely occurs at the reducing end of the disaccharide, with Glu333 possibly acting as the general base.

Amino Acid Sequence↗
PubMed1999

HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions.

Cancer predisposition in hereditary non-polyposis colon cancer (HNPCC) is caused by defects in DNA mismatch repair (MMR). Mismatch recognition is attributed to two heterodimeric protein complexes: MutSalpha (refs 2, 3, 4, 5), a dimer of MutS homologues MSH2 and MSH6; and MutSbeta (refs 2,7), a dimer of MSH2 and MSH3. These complexes have specific and redundant mismatch recognition capacity. Whereas MSH2 deficiency ablates the activity of both dimers, causing strong cancer predisposition in mice and men, loss of MSH3 or MSH6 (also known as GTBP) function causes a partial MMR defect. This may explain the rarity of MSH6 and absence of MSH3 germline mutations in HNPCC families. To test this, we have inactivated the mouse genes Msh3 (formerly Rep3 ) and Msh6 (formerly Gtmbp). Msh6-deficient mice were prone to cancer; most animals developed lymphomas or epithelial tumours originating from the skin and uterus but only rarely from the intestine. Msh3 deficiency did not cause cancer predisposition, but in an Msh6 -deficient background, loss of Msh3 accelerated intestinal tumorigenesis. Lymphomagenesis was not affected. Furthermore, mismatch-directed anti-recombination and sensitivity to methylating agents required Msh2 and Msh6, but not Msh3. Thus, loss of MMR functions specific to Msh2/Msh6 is sufficient for lymphoma development in mice, whereas predisposition to intestinal cancer requires loss of function of both Msh2/Msh6 and Msh2/Msh3.

Alleles↗
PubMed1995

Proprioceptive sensory codes mediating movement trajectory perception: human hand vibration-induced drawing illusions.

To study the organization of the proprioceptive sensory codes subserving movement trajectory perception, complex hand drawing illusions were elicited using various vibration patterns applied to the wrist muscles of nine human subjects. It was established that it is possible to elicit kinesthetic illusions involving spatially oriented lines and geometrical shapes such as rectilinear or curvilinear figures by activating four groups of muscle tendons at the wrist level. The vibration sequences specifically evoking each shape were determined by varying the vibration frequency, the duration of each stimulus applied, and the vibrator onsets, and by applying the vibrations either successively or simultaneously. The proprioceptive coding of a trajectory can be modelled in terms of a series of vectors, the direction of which depends on the anatomical sites of the muscles that are stretched and shortened during the movement. The vector giving the spatial path of a movement is the sum vector of the vectors determined on the basis of the proprioceptive inputs originating from each muscle, and the modulus of the resulting vector is the instantaneous velocity of the movement. In line with previous cortical data, our results suggest that the perception of the spatial paths of limb segment movements is coded in joint space kinematic coordinates on the basis of the relevant ongoing proprioceptive information. It therefore emerges from the results of this study that muscle proprioception is able to generate spatiotemporal afferent patterns that may mediate complex cognitive operations such as those involved in the memorizing and recognition of motor forms.

Female↗
PubMed2004

Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents?

According to traditional thinking, atherosclerosis results from passive lipid deposition in the vascular wall. Thus, therapies predominantly targeted lipid metabolism. The contemporary view of atherosclerosis, however, has broadened to include an active and complex role for inflammation, orchestrated in part by mediators of the immune system. This recognition prompted the question of whether antiinflammatory interventions might provide a novel avenue for the treatment of atherosclerosis. Uncertainties about the type of antiinflammatory regimen and appropriate patient selection currently hamper clinical investigation. Yet cardiovascular scientists have begun to address these questions at the bench, in experimental models, and indirectly in humans. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA reductase (statins) have emerged as promising tools with dual functions. Originally designed to target elevated lipids, the "traditional" cause of atherosclerosis, statins might also confer cardiovascular benefit by directly or indirectly modulating the inflammatory component of this prevalent disease. Yet controversy persists regarding the (clinical) relevance of these potential non-LDL-lowering "pleiotropic" functions of statins. This overview addresses the controversy by reviewing in vitro and in vivo evidence regarding statins as antiinflammatory agents.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Susceptibility to rheumatoid arthritis--the conformational equivalence hypothesis.

The occurrence of the inappropriate immune response of rheumatoid arthritis is likely controlled by several alleles of class II DR beta chain genes of the major histocompatibility complex (MHC). These include certain of those that encode the serologically distinct DR1 and DR4 specificities. In a manner analogous to a segregation analysis, advantage was taken of ethnic differences in susceptibility associated with different alleles and parallel differences in the organization of the class II haplotypes that specify either similar or divergent serologic specificities. This permitted mapping of this disease susceptibility into a single equivalent polymorphic alpha helical conformation shared by each DR beta allelic product. This suggests that rheumatoid arthritis originates from a unitary immune recognition event initiated by particular class II MHC molecules.

Amino Acid Sequence↗
PubMed2006

Comparison of derivative preprocessing and automated polynomial baseline correction method for classification and quantification of narcotics in solid mixtures.

This work offers a real-world comparison of derivative preprocessing and a new polynomial method described by Lieber and Mahadevan-Jansen (LMJ) for baseline correction of Raman spectra with widely varying backgrounds. This comparison is based on their outcomes in factor analysis, analyte discrimination, and quantification. Both correction methods are applied to a Raman spectra data set taken from 85 solid samples of illegal narcotics diluted with various materials. It is found that neither approach outperforms the other, as they give similar principal component analysis (PCA) models and quantification errors: cocaine and heroin show cross-validation errors of approximately 8%, while MDMA is quantified to a cross-validation error of approximately 3-4%. The LMJ method does offer several other advantages, the most significant being the retention of original peak shapes after the correction, which simplifies the interpretation of the preprocessed spectra. The LMJ method is therefore recommended for use as a baseline correction method in future research with Raman spectroscopy.

Algorithms↗
PubMed1999

Clinical aspects, epidemiology, and prognosis of atopic dermatitis.

OBJECTIVE: This review article examines the clinical aspects, epidemiology, and prognosis of atopic dermatitis. DATA SOURCES: These are studies and review articles from textbooks of dermatitis and allergy in general, as well as more recent epidemiologic surveys published in specialist journals of allergy and dermatology. STUDY SELECTION: Included studies meet the criteria of being a survey of the prevalence of atopic dermatitis published recently in a respected peer-reviewed journal. Particular emphasis is placed on those that examine both the prevalence of the problem and significant causative and associated factors. RESULTS: Atopic dermatitis is frequently a severe illness that develops in early infancy. It can persist beyond the childhood years and is often found in association with significant respiratory complications. The exact pathogenesis is unclear but it appears that it has a complex immunologic origin. Early surveys lack the methodologic refinements of more recent data from the mid-1990s, including the SCARPOL study. Collectively, these point to a high current prevalence rate of 10% to 15%, a figure that has risen steadily in the preceding decades. The most common associations of atopic dermatitis are a risk of developing respiratory disorders, such as allergic rhinitis and asthma (40% to 60%), and a persistence rate after puberty (40% to 60%), which is indeed much higher than previously suspected. CONCLUSIONS: A clear recognition of the various disease subgroups along with intervention studies that evaluate reduction of risk are needed before more precise treatment strategies can be devised.

Adolescent↗
PubMed1998

The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT.

Virtually all diffuse large cell lymphomas and a significant fraction of follicular lymphomas contain translocations and/or point mutations in the 5' non-coding region of the putative oncogene BCL-6, that are presumed to deregulate its expression. BCL-6 encodes a Cys2-His2 zinc finger transcriptional repressor with a POZ domain at its amino-terminus. The POZ (or BTB) domain, a 120-amino-acid motif, mediates homomeric and, in some proteins, heteromeric POZ-POZ interactions. In addition, the POZ domain is required for transcriptional repression of several proteins, including BCL-6. Using a yeast two-hybrid screen, we identified N-CoR and SMRT as BCL-6 interacting proteins. Both N-CoR and SMRT, which were originally identified as co-repressors for the unliganded nuclear thyroid hormone and retinoic acid receptors, are components of large complexes containing histone deacetylases. We show that the interaction between BCL-6 and these co-repressors is also detected in the more physiologically relevant mammalian two-hybrid assay. The POZ domain is necessary and sufficient for interaction with these co-repressors. BCL-6 and N-CoR co-localize to punctate regions of the nucleus. Furthermore, when BCL-6 is bound to its consensus recognition sequence in vivo, it can interact with N-CoR and SMRT. We find, in vitro, that POZ domains from a variety of other POZ domain-containing proteins, including the transcriptional repressor PLZF, as well as ZID, GAGA and a vaccinia virus protein, SalF17R, also interact with varying affinities with N-CoR and SMRT. We find that BCL-6 POZ domain mutations that disrupt the interaction with N-CoR and SMRT no longer repress transcription. In addition, these mutations no longer self associate suggesting that self interaction is required for interaction with the co-repressors and for repression. More recently N-CoR has also been implicated in transcriptional repression by the Mad/Mxi proteins. Our demonstration that N-CoR and SMRT interact with the POZ domain containing proteins indicates that these co-repressors are likely involved in the mediation of repression by multiple classes of repressors and may explain, in part, how POZ domain containing repressors mediate transcriptional repression.

Amino Acid Sequence↗
PubMed1990

Transcription factors NFI and NFIII/oct-1 function independently, employing different mechanisms to enhance adenovirus DNA replication.

Initiation of adenovirus DNA replication is strongly enhanced by two transcription factors, nuclear factor I (NFI) and nuclear factor III (NFIII/oct-1). These proteins bind to two closely spaced recognition sequences in the origin. We produced NFI and NFIII/oct-1, as well as their biologically active, replication-competent DNA-binding domains (NFI-BD and the POU domain), in a vaccinia virus expression system and purified these polypeptides to apparent homogeneity. By DNase I footprinting and gel retardation, we show that the two proteins, as well as their purified DNA-binding domains, bind independently and without cooperative effects to their recognition sequences. By using a reconstituted system consisting of the purified viral proteins (precursor terminal protein-DNA polymerase complex (pTP-pol) and DNA-binding protein, we show that NFIII/oct-1 or the POU domain stimulates DNA replication in the absence of NFI or NFI-BD and vice versa. When added together, the enhancing effect of the two transcription factors was independent and nonsynergistic. Interestingly, stimulation by NFI or NFI-BD was strongly dependent on the concentration of the pTP-pol complex. At low pTP-pol concentrations, NFI or NFI-BD stimulated up to 50-fold, while at high concentrations, the stimulation was less than twofold, indicating that the need for NFI can be overcome by high pTP-pol concentrations. In contrast, stimulation by NFIII/oct-1 or the POU domain was much less dependent on the pTP-pol concentration. These data support a model in which NFI enhances initiation through an interaction with pTP-pol. Glutaraldehyde cross-linking experiments indicate contacts between pTP-pol and NFI but not NFIII/oct-1. The site of interaction is located in the NFI-BD domain.

Adenoviruses, Human↗
PubMed1992

A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization.

The p53 gene product has been implicated in both human and animal tumorigenesis. p53 forms heterologous complexes with the transforming proteins encoded by several different DNA tumor viruses. p53 also assembles into stable homo-oligomers. We demonstrate that the major structural determinant for the tetramerization of p53 is an alpha-helical plus basic region motif near the C-terminus of the protein. A monomeric p53 mutant adopts a conformation distinct from both 'wild-type' and 'mutant' form as defined by PAb1620 and PAb240 monoclonal antibody recognition. Nevertheless, monomeric and dimeric mutant p53 proteins retain the ability to suppress SV40 origin-directed DNA replication in vivo. Thus, p53-p53 interaction and expression of the PAb1620 epitope is not a prerequisite for such activity. We present data suggesting that suppression of replication by p53 may occur by a mechanism that is independent of detectable p53-T antigen association.

Amino Acid Sequence↗
PubMed1997

Recognition of porcine major histocompatibility complex class I antigens by human CD8+ cytolytic T cell clones.

To evaluate the nature of the human cellular immune response to porcine xenoantigens, cytolytic T lymphocyte (CTL) cell lines were generated against porcine aortic endothelial cells (PAEC). After four stimulations, the phenotypes of the T cell lines were primarily CD8+ (79.7+/-19.6%). Natural killer cells were not detected. Functional analysis of the T cell lines showed specific cytotoxicity against syngeneic porcine targets with no lysis of unrelated porcine cells, human cells, or K562, a natural killer target. The major histocompatibility complex (MHC) specificity of this response was confirmed when T cell lines established against PAEC from partially inbred SLAdd miniature swine lysed only PAEC and phytohemagglutinin-stimulated lymphocytes from SLAdd origin but not SLAgg targets. Both CD8+ (7/12) and CD4+ (5/12) T cell clones were generated from the bulk cell lines. All of the CD8+ T cell clones specifically lysed stimulator PAEC and swine leukocyte antigen (SLA)-matched, phytohemagglutinin-stimulated lymphocyte targets but not unrelated porcine targets. CD4+ T cell clones, as expected, showed no lysis of any porcine target cells. The lysis of porcine targets by the human CD8+ cytotoxic T lymphocyte clones was inhibited by monoclonal antibodies against SLA class I antigens and human CD8, which indicates that human CD8+ T cells recognize porcine MHC class I molecules. These results, which show that human T cells differentiate between porcine MHC alleles, have relevance in the clinical application of xenografts.

Animals↗
PubMed1984

Adult Still's disease. Evolution of a clinical syndrome and diagnosis, treatment, and follow-up of 17 patients.

Adult Still's Disease (SD) has evolved into a well-characterized nosologic entity. This categorization allows physicians to place a unifying label on the rare, puzzling patient who presents with a systemic illness characterized by high spiking fever of unknown cause associated with intense arthralgias or arthritis, an evanescent erythematous macular or maculopapular rash, and other less constant features of systemic illness including lymphadenopathy, hepatosplenomegaly, sore throat, leukocytosis, anemia and elevated concentration of hepatic enzymes. The diagnosis of Adult SD is syndromic, based solely on compatible clinical findings; serologic or other diagnostic tests do not aid in diagnosis. The diagnostic problem presented by these patients with such severe systemic illness and the insecurities inherent in diagnosis based solely on clinical features make the availability of the diagnosis, Adult SD, useful in patient care. The cause of Adult SD is unknown. Some have speculated that the disease has features of non-necrotizing immune complex vasculitis. Rubella infection has been reported to be associated with Adult SD, but no clear-cut etiologic relationship has been established. Neither rubella infection nor any other potential antigen has been identified consistently in association with the disease. Management of patients with the disease depends on the correct diagnosis. Diagnosis should include recognition of the syndrome as well as exclude other possible diseases. Control of systemic manifestations may require unusually high doses of aspirin, indomethacin or other non-steroidal anti-inflammatory drugs, prednisone or combinations of these drugs. Some adults appear to require both high-dose prednisone and indomethacin to control disease manifestations. Fortunately, systemic attacks are usually episodic; steroid toxicity can be minimized by use of alternate day doses and attempts to discontinue steroids between episodes. The current series and other reports of long-term follow-up indicate that Adult SD may be more disabling than was originally reported. At least three patterns of recurrences occur: 1) systemic attacks with or without arthritis, 2) pauciarticular disease, and 3) disabling deforming chronic arthritis, which may require surgery and long-term anti-inflammatory, gold, or cytotoxic therapy.

Adolescent↗
PubMed1989

Histone H1(0) mapping using monoclonal antibodies.

Monoclonal antibodies (mAb) to ox liver histone H1 degree were produced and characterized. Two sets of mice were immunized either with pure H1(0) or with an H1(0)-yeast tRNA complex. Eleven hybridomas of various clonal origin were selected. Typing of the antibodies indicated that all but three IgM belonged to the IgG1 class and contained kappa light chains. Immunoblotting experiments using peptides derived from H1(0) or H5 treated by various proteolytic agents (trypsin, N-bromosuccinimide, cyanogen bromide, acetic acid), revealed that nine of the mAb reacted with the globular part of H1(0). More advanced characterization of the antigenic determinants allowed us to determine distinct regions within this globular part which are involved in the antigenic recognition. The peptopes could be subdivided into two groups. Three mAb bound to residues 24-27 and were specific for H1(0). Six mAb bound to residues 27-30 and were specific for H1(0) except one of them which strongly cross-reacted with H5 and GH5. Two mAb reacted with the entire histone H1(0) but failed to react with any of the peptides, suggesting that the corresponding epitope is a conformational antigenic determinant. In order to confirm the localization of the two distinct regions which are involved in the antigenic recognition, a synthetic decapeptide corresponding to the beginning of human H1(0) globular part (from residue 19 to residue 28) was synthesized. Inhibition experiments of the reaction between H1(0) and the various IgG1 mAb by increasing amounts of peptide-bovine serum albumin conjugates were then performed.

Amino Acid Sequence↗