ABSTRACT
Binding of the BAG domain to the eukaryotic chaperone heat-shock protein (Hsp70) promotes ATP-dependent release of the protein substrate from Hsp70. Although the murine and human BAG domains have been shown to form an antiparallel three-helix bundle, the Caenorhabditis elegans BAG domain is formed by two antiparallel helices, while the third helix is extended away and stabilized by crystal-packing interactions. A small beta-sheet between helices 2 and 3 interferes with formation of the intramolecular three-helix bundle. However, intermolecular three-helix bundles are observed throughout the crystal packing and suggest that stable functional dimers and tetramers can be formed in solution. The structure may represent a new folding type of the BAG domain.
Subject(s)
Caenorhabditis elegans Proteins/chemistry , Caenorhabditis elegans/chemistry , Genes, bcl-2/genetics , HSP70 Heat-Shock Proteins/chemistry , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Crystallization , Genomics , HSP70 Heat-Shock Proteins/genetics , Models, Molecular , Molecular Sequence Data , Protein Conformation , Robotics , X-Ray DiffractionABSTRACT
Among theories of biological underpinnings to personality traits, different mechanisms of the serotonergic system are perhaps the most common factors suggested to influence individual differences in personality traits. We have investigated two frequent variants in the serotonin 2A receptor gene (5-HT2A) and personality traits. Healthy Swedish subjects (n = 304) were assessed with the Karolinska Scales of Personality (KSP) inventory. After correction for multiple testing, no significant differences were found. We conclude that the investigated 5-HT2A gene variants do not significantly influence personality as assessed by the KSP in the present population.
Subject(s)
Genetic Variation , Receptors, Serotonin/genetics , Adult , Female , Humans , Interviews as Topic , Male , Middle Aged , Personality/genetics , Personnel, Hospital , Receptor, Serotonin, 5-HT2A , Reverse Transcriptase Polymerase Chain Reaction , Students , Surveys and QuestionnairesABSTRACT
We have examined the imprinting status of the serotonin-2A (5-HT2A) receptor gene (HTR2A) in a series of 41 tissue samples from human adult brain. Using a HpaII RFLP polymorphism in the coding region, we obtained evidence of monoallelic expression of HTR2A in 4 out of 18 informative individuals. However, biallelic expression of HTR2A was observed in other individuals (14/18), suggesting that within the human population HTR2A imprinting in brain is polymorphic.
Subject(s)
Brain/metabolism , Genomic Imprinting , Polymorphism, Genetic , Receptors, Serotonin/genetics , Alleles , Humans , Polymerase Chain Reaction , Receptor, Serotonin, 5-HT2AABSTRACT
Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated the possible relationships between DNA polymorphisms in the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) genes and CSF concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 66). The DAT polymorphism was not significantly associated with any of the monoamine metabolites, but a tendency for relationship with 5-HIAA was found in women. For both of the two SERT polymorphisms investigated, a functional promoter polymorphism and an intronic polymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT polymorphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not HVA and 5-HIAA concentrations. The results suggest that SERT and NET genotypes may participate differentially in the regulation of the norepinephrine turnover rate under presumed steady-state conditions in the central nervous system. As only limited data so far indicate interactions between the serotonin and norepinephrine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpreted with caution until replicated.
Subject(s)
Biogenic Monoamines/metabolism , Carrier Proteins/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Nerve Tissue Proteins , Polymorphism, Genetic , Symporters , Adult , Analysis of Variance , Biogenic Monoamines/cerebrospinal fluid , Biogenic Monoamines/genetics , Brain Chemistry/genetics , Cohort Studies , Dopamine Plasma Membrane Transport Proteins , Female , Genotype , Homovanillic Acid/cerebrospinal fluid , Humans , Hydroxyindoleacetic Acid/cerebrospinal fluid , Male , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Middle Aged , Norepinephrine Plasma Membrane Transport Proteins , Phenotype , Polymerase Chain Reaction , Serotonin Plasma Membrane Transport Proteins , Sex FactorsSubject(s)
Polymorphism, Genetic , Receptors, Serotonin/genetics , Schizophrenia/genetics , Alleles , Genotype , HumansSubject(s)
Fibrinogen/isolation & purification , Animals , Cells, Cultured , Chromatography, Ion Exchange/methods , Culture Techniques/methods , Enzyme-Linked Immunosorbent Assay , Fibrinogen/analysis , Fibrinogen/biosynthesis , Indicators and Reagents , Liver/metabolism , Liver Neoplasms, Experimental/metabolism , Macromolecular Substances , RatsABSTRACT
Hepatocyte stimulating factor is a monocyte derived protein which regulates hepatic plasma protein synthesis. Human hepatocyte stimulating factor was purified to apparent homogeneity from adherent peripheral blood monocytes by using ion exchange, gel permeation and reversed phase chromatography. Electrophoretic analysis showed that it has a Mr of 28,000 daltons and an isoelectric point of 5.4. Biological assays specific for hepatocyte stimulating factor and interleukin-1 showed that they are distinct and have independent biological effects.