Abstract:
:Heme is an essential prosthetic group of proteins involved in oxygen transport, energy metabolism and nitric oxide production. ALAS1 (5-aminolevulinate synthase) is the rate-limiting enzyme in heme synthesis in the liver and is highly regulated to adapt to the metabolic demand of the hepatocyte. In the present study, we describe human hepatic ALAS1 as a new direct target for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). In primary human hepatocytes and in HepG2 cells, PPARalpha agonists induced an increase in ALAS1 mRNA levels, which was abolished by PPARalpha silencing. These effects are mediated by two functional PPAR binding sites at positions -9 and -2.3 kb relative to the ALAS1 transcription start site. PPARalpha ligand treatment also up-regulated the mRNA levels of the genes ALAD (5-aminolevulinate dehydratase), UROS (uroporphyrinogen III synthase), UROD (uroporphyrinogen decarboxylase), CPOX (coproporphyrinogen oxidase) and PPOX (protoporphyrinogen oxidase) encoding for enzymes controlling further steps in heme biosynthesis. In HepG2 cells treated with PPARalpha agonists and in mouse liver upon fasting, the association of PPARalpha, its partner retinoid X receptor, PPARgamma co-activator 1alpha and activated RNA polymerase II with the transcription start site region of all six genes was increased, leading to higher levels of the metabolite heme. In conclusion, these data strongly support a role of PPARalpha in the regulation of human ALAS1 and of five additional genes of the pathway, consequently leading to increased heme synthesis.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Degenhardt T,Väisänen S,Rakhshandehroo M,Kersten S,Carlberg Cdoi
10.1016/j.jmb.2009.03.024subject
Has Abstractpub_date
2009-05-01 00:00:00pages
225-38issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(09)00304-0journal_volume
388pub_type
杂志文章,收录出版abstract::Solution NMR structures for sperm whale carbonmonoxy myoglobin have been calculated using 1301 distance restraints determined from nuclear Overhauser enhancement (NOE) measurements on 15N-labeled protein and chemical shift calculations for 385 protons. Starting structures included four crystal forms of myoglobin and 1...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1718
更新日期:1994-11-25 00:00:00
abstract::The intergenic region in the genome of the Ff class of filamentous phage (comprising strains fl, fd and M13) genome constitutes 8% of the viral genome, and has essential functions in DNA replication and phage morphogenesis. The functional domains of this region may be inserted into separate sites of a plasmid to funct...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90858-h
更新日期:1992-12-05 00:00:00
abstract::The Saccharomyces cerevisiae non-Mendelian factor [URE3] propagates by a prion-like mechanism, involving aggregation of the chromosomally encoded protein Ure2. The N-terminal prion domain (PrD) of Ure2 is required for prion activity in vivo and amyloid formation in vitro. However, the molecular mechanism of the prion-...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.5234
更新日期:2002-01-11 00:00:00
abstract::Using a lacI-Z fusion system, we have determined the efficiency of suppression of nonsense codons in the I gene of Escherichia coli by assaying beta-galactosidase activity. We examined the efficiency of four amber suppressors acting on 42 different amber (UAG) codons at known positions in the I gene, and the efficienc...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(83)90087-6
更新日期:1983-02-15 00:00:00
abstract::Kinesin superfamily molecular motors step along microtubules (MTs) via a cycle of conformational changes which is coupled to ATP turnover. To probe the coupling mechanism, we titrated the effects of various nucleotides on MT binding by two superfamily members; MT plus-end-directed kinesin and MT minus-end-directed non...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0147
更新日期:1996-03-22 00:00:00
abstract::Protein aggregation underlies an increasing number of human diseases. Recent experiments have shown that the aggregation reaction is exquisitely specific involving particular interactions between non-native proteins. However, aggregation of certain proteins, for example beta-amyloid, in vivo leads to the recruitment o...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.11.062
更新日期:2007-02-16 00:00:00
abstract::The pathological Aβ aggregates associated with Alzheimer's disease follow a nucleation-dependent path of formation. A nucleus represents an oligomeric assembly of Aβ peptides that acts as a template for subsequent incorporation of monomers to form a fibrillar structure. Nuclei can form de novo or via surface-catalyzed...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2018.06.005
更新日期:2018-08-17 00:00:00
abstract::The bacteriophage T4 replication origins ori(uvsY) and ori(34) each contain two distinct components: a T4 middle-mode promoter that is strictly required for replication and a downstream region of about 50 bp that is required for maximal levels of replication. Here, we present evidence that structure of the downstream ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0844
更新日期:1997-03-14 00:00:00
abstract::Adenoviruses are respiratory, ocular and enteric pathogens that form complex capsids, which are assembled from seven different structural proteins and composed of several core proteins that closely interact with the packaged dsDNA genome. The recent near-atomic resolution structures revealed that the interlacing conti...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2017.06.025
更新日期:2017-09-01 00:00:00
abstract::Recombinant expression systems differ in the type of glycosylation they impart on expressed antigens such as the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, potentially affecting their biological properties. We performed head-to-head antigenic, immunogenic and molecular profiling of two distant...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.08.033
更新日期:2010-10-15 00:00:00
abstract::Membranes have a potent ability to promote secondary structure formation in a wide range of membrane-active peptides, believed to be due to a reduction through hydrogen bonding of the energetic cost of partitioning peptide bonds. This process is of fundamental importance for understanding the mechanism of action of to...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2346
更新日期:1999-01-29 00:00:00
abstract::A database of X-ray crystal structures of double helical DNA oligomers has been used to analyse the role of the sugar-phosphate backbone in coupling the conformational properties of neighbouring dinucleotide steps. The base step parameters which are most strongly coupled to the backbone degrees of freedom are slide an...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.3237
更新日期:2000-01-07 00:00:00
abstract::The X-ray structures of two hemoglobins (Hb) from the sea cucumber Caudina arenicola (an echinoderm) have been determined: a low spin, hemichrome, monomeric Hb-C chain, and a cyanomet-liganded dimeric Hb-D chain. Attempts to obtain crystal structures of the deoxy-liganded and hemichrome forms from the same chain type ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1995.0445
更新日期:1995-08-18 00:00:00
abstract::Using homopolymeric units of either phenylalanine or tryptophan to replace the natural core segment of the Escherichia coli alkaline phosphatase signal peptide, the hydrophobicity requirements for protein export and processing were further explored. The mutant signal peptide containing polyphenylalanine functioned at ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90577-7
更新日期:1992-03-05 00:00:00
abstract::Bacteriorhodopsin is the smallest autonomous light-driven proton pump. Proposals as to how it achieves the directionality of its trans-membrane proton transport fall into two categories: accessibility-switch models in which proton transfer pathways in different parts of the molecule are opened and closed during the ph...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00903-3
更新日期:2003-10-03 00:00:00
abstract::Rearrangement of actin filaments by polymerization, depolymerization, and severing is important for cell locomotion, membrane trafficking, and many other cellular functions. Cofilin and actin-interacting protein 1 (AIP1; also known as WDR1) are evolutionally conserved proteins that cooperatively sever actin filaments....
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2018.11.010
更新日期:2019-01-18 00:00:00
abstract::Crystal structures of two complexes between recombinant MS2 capsids and RNA operator fragments have been determined at 2.7 A resolution. The coat protein of the RNA bacteriophage MS2 is bifunctional; it forms the icosahedral virus shell to protect the viral nucleic acid and it acts as a translational repressor by bind...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1144
更新日期:1997-08-01 00:00:00
abstract::Mitochondrial DNA (mtDNA) sequence variation can influence the penetrance of complex diseases and climatic adaptation. While studies in geographically defined human populations suggest that mtDNA mutations become fixed when they have conferred metabolic capabilities optimally suited for a specific environment, it has ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2014.02.009
更新日期:2014-05-29 00:00:00
abstract::It has been well established that a single amino acid sequence can give rise to several conformationally distinct amyloid states. The extent to which amyloid structures formed within the same sequence are different, however, remains unclear. To address this question, we studied two amyloid states (referred to as R- an...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.05.051
更新日期:2010-07-23 00:00:00
abstract::The beta-globin gene cluster of human, gorilla and chimpanzee contain the same number and organization of beta-type globin genes: 5'-epsilon (embryonic)-G gamma and A gamma (fetal)-psi beta (inactive)-delta and beta (adult)-3'. We have isolated the psi beta-globin gene regions from the three species and determined the...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(84)90256-0
更新日期:1984-12-25 00:00:00
abstract::Alphavirus replicons are very useful for analyzing different aspects of viral molecular biology. They are also useful tools in the development of new vaccines and highly efficient expression of heterologous genes. We have investigated the translatability of Sindbis virus (SV) subgenomic mRNA bearing different 5'-untra...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.07.014
更新日期:2010-09-10 00:00:00
abstract::The decrease in conformational stability, delta(delta G), has been measured for 72 aliphatic side-chain mutants from four proteins in which a larger side-chain is replaced by a smaller side-chain so that steric effects are minimal. When these delta(delta G) values are corrected to the same accessibility, namely 100% b...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90121-y
更新日期:1992-07-05 00:00:00
abstract::The bacterial flagellar motor is a rotary motor in the cell envelope of bacteria that couples ion flow across the cytoplasmic membrane to torque generation by independent stators anchored to the cell wall. The recent observation of stepwise rotation of a Na(+)-driven chimeric motor in Escherichia coli promises to reve...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.12.023
更新日期:2008-03-07 00:00:00
abstract::Protein-primed DNA polymerases form a subgroup of the eukaryotic-type DNA polymerases family, also called family B or alpha-like. A multiple amino acid sequence alignment of this subgroup of DNA polymerases led to the identification of two insertions, TPR-1 and TPR-2, in the polymerisation domain. We showed previously...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00788-5
更新日期:2003-08-22 00:00:00
abstract::Solvent binding in the nucleosome core particle containing a 147 base pair, defined-sequence DNA is characterized from the X-ray crystal structure at 1.9 A resolution. A single-base-pair increase in DNA length over that used previously results in substantially improved clarity of the electron density and accuracy for ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/S0022-2836(02)00386-8
更新日期:2002-06-21 00:00:00
abstract::The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurem...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.12.021
更新日期:2014-03-06 00:00:00
abstract::The nine polyglutamine (polyQ) neurodegenerative diseases are caused in part by a gain-of-function mechanism involving protein misfolding, the deposition of β-sheet-rich aggregates and neuronal toxicity. While previous experimental evidence suggests that the polyQ-induced misfolding mechanism is context dependent, the...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.09.014
更新日期:2011-11-04 00:00:00
abstract::The steps of UUC recognition by tRNAPhe were analysed by temperature-jump measurements. At ion concentrations close to physiological conditions we found three relaxation processes, which we assigned to (1) formation of codon-anticodon complexes, (2) a conformational change of the anticodon loop coupled with Mg2+ bindi...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(84)90085-8
更新日期:1984-04-25 00:00:00
abstract::Ricin is a potent cytotoxin which has been used widely in the construction of therapeutic agents such as immunotoxins. Recently it has been used by governments and underground groups as a poison. There is interest in identifying and designing effective inhibitors of the ricin A chain (RTA). In this study computer-assi...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0865
更新日期:1997-03-14 00:00:00
abstract::The anti-breast tumour antibody SM3 has a high selectivity in reacting specifically with carcinoma-associated mucin. SM3 recognises the core repeating motif (Pro-Asp-Thr-Arg-Pro) of aberrantly glycosylated epithelial mucin MUC1, and has potential as a therapeutic and diagnostic tool. Here we report the crystal structu...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2209
更新日期:1998-12-04 00:00:00