Dissociation of apolipoprotein E oligomers to monomer is required for high-affinity binding to phospholipid vesicles.


:The apolipoprotein apoE plays a key role in cholesterol and lipid metabolism. There are three isoforms of this protein, one of which, apoE4, is the major risk factor for Alzheimer's disease. At micromolar concentrations all lipid-free apoE isoforms exist primarily as monomers, dimers, and tetramers. However, the molecular weight form of apoE that binds to lipid has not been clearly defined. We have examined the role of self-association of apoE with respect to interactions with phospholipids. Measurements of the time dependence of turbidity clearance of small unilamellar vesicles of dimyristoyl-sn-glycero-3-phosphocholine (DMPC) upon addition of apoE show that higher molecular weight oligomers bind poorly if at all. The kinetic data can be described by a reaction model in which tetramers and dimers of apoE must first dissociate to monomers which then bind to the liposome surface in a fast and reversible manner. A slow but not readily reversible conformational conversion of the monomer then occurs. Prior knowledge of the rate constants for the association-dissociation process allows us to determine the rate constant of the conformational conversion. This rate constant is isoform dependent and appears to correlate with the stability of the apoE isoforms with the rate of dissociation of the apoE oligomers to monomers being the rate-limiting process for lipidation. Differences in the lipidation kinetics between the apoE isoforms arise from their differences in the self-association behavior leading to the conclusion that self-association behavior may influence biological functions of apoE in an isoform-dependent manner.






Garai K,Baban B,Frieden C




Has Abstract


2011-04-05 00:00:00












  • Mass spectrometric characterization of the human androgen receptor ligand-binding domain expressed in Escherichia coli.

    abstract::The ligand-binding domain (LBD) of the human androgen receptor (hAR LBD), encompassing amino acids (AAs) 647-919, was expressed in Escherichia coli with an N-terminal polyhistidine tag (His(10)-hAR LBD) from a pET-16b vector. The overexpressed protein was initially insoluble in inclusion bodies, and was subsequently s...


    pub_type: 杂志文章


    authors: Zhu Z,Becklin RR,Desiderio DM,Dalton JT

    更新日期:2001-09-11 00:00:00

  • Role of arginine-163 and the 163REEK166 motif in the oligomerization of truncated alpha A-crystallins.

    abstract::To gain insight into the mechanism by which Arg-163 influences oligomerization of alphaA-crystallin, we prepared a series of truncated alphaA-crystallins with or without mutation of the Arg-163 residue. Expression of the proteins was achieved in Escherichia coli BL21 (DE3) pLysS cells, and alphaA-crystallin was purifi...


    pub_type: 杂志文章


    authors: Rajan S,Chandrashekar R,Aziz A,Abraham EC

    更新日期:2006-12-26 00:00:00

  • Secondary structure of the ETS domain places murine Ets-1 in the superfamily of winged helix-turn-helix DNA-binding proteins.

    abstract::The members of the ets gene family of transcription factors are characterized by a conserved 85-residue DNA-binding region, termed the ETS domain, that lacks sequence homology to structurally characterized DNA-binding motifs. The secondary structure of the ETS domain of murine Ets-1 was determined on the basis of NMR ...


    pub_type: 杂志文章


    authors: Donaldson LW,Petersen JM,Graves BJ,McIntosh LP

    更新日期:1994-11-22 00:00:00

  • Thermodynamics of ligand binding to trp repressor.

    abstract::The thermodynamics of L-tryptophan and operator DNA binding to the tryptophan repressor of Escherichia coli were analyzed by titration microcalorimetry and van't Hoff analysis of footprinting titrations, respectively. At 25 degrees C in 10 mM sodium phosphate, pH 7.6, and 0.1 M NaCl, the binding of L-tryptophan to the...


    pub_type: 杂志文章


    authors: Jin L,Yang J,Carey J

    更新日期:1993-07-20 00:00:00

  • Substrate binding and catalytic mechanism in ascorbate peroxidase: evidence for two ascorbate binding sites.

    abstract::The catalytic mechanism of recombinant soybean cytosolic ascorbate peroxidase (rsAPX) and a derivative of rsAPX in which a cysteine residue (Cys32) located close to the substrate (L-ascorbic acid) binding site has been modified to preclude binding of ascorbate [Mandelman, D., Jamal, J., and Poulos, T. L. (1998) Bioche...


    pub_type: 杂志文章


    authors: Lad L,Mewies M,Raven EL

    更新日期:2002-11-19 00:00:00

  • Proline for alanine substitutions in the C-peptide helix of ribonuclease A.

    abstract::The effect on overall alpha-helix content of substituting proline for alanine has been determined at 5 positions (1, 2, 4, 5, and 13) of a 13-residue peptide related in sequence to residues 1-13 of ribonuclease A. The helix content falls off rapidly as proline is moved inward, and the proline residue effectively trunc...


    pub_type: 杂志文章


    authors: Strehlow KG,Robertson AD,Baldwin RL

    更新日期:1991-06-11 00:00:00

  • The crystal structure of the Escherichia coli maltodextrin phosphorylase-acarbose complex.

    abstract::Acarbose is a naturally occurring pseudo-tetrasaccharide. It has been used in conjunction with other drugs in the treatment of diabetes where it acts as an inhibitor of intestinal glucosidases. To probe the interactions of acarbose with other carbohydrate recognition enzymes, the crystal structure of E. coli maltodext...


    pub_type: 杂志文章


    authors: O'Reilly M,Watson KA,Johnson LN

    更新日期:1999-04-27 00:00:00

  • Structure-function relationships of scorpion neurotoxins.

    abstract::Chemical modification of some trifunctional amino acid residues in toxins I, II, and III of the scorpion Androctonus australis Hector have been performed. The results indicate: (1) Reduction and methylation of one disulfide bridge destroy toxic activity of toxin II. (2) The only tryptophan residue of toxin II (positio...


    pub_type: 杂志文章


    authors: Habersetzer-Rochat C,Sampieri F

    更新日期:1976-06-01 00:00:00

  • The affinity of elongation factor Tu for an aminoacyl-tRNA is modulated by the esterified amino acid.

    abstract::When different mutations were introduced into the anticodon loop and at position 73 of YFA2, a derivative of yeast tRNA(Phe), a single tRNA body was misacylated with 13 different amino acids. The affinities of these misacylated tRNAs for Thermus thermophilus elongation factor Tu (EF-Tu).GTP were determined using a rib...


    pub_type: 杂志文章


    authors: Dale T,Sanderson LE,Uhlenbeck OC

    更新日期:2004-05-25 00:00:00

  • Elastin binds to a multifunctional 67-kilodalton peripheral membrane protein.

    abstract::Elastin binding proteins from plasma membranes of elastin-producing cells were isolated by affinity chromatography on immobilized elastin peptides. Three proteins of 67, 61, and 55 kDa were released from the elastin resin by guanidine/detergent, soluble elastin peptides, synthetic peptide VGVAPG, or galactoside sugars...


    pub_type: 杂志文章


    authors: Mecham RP,Hinek A,Entwistle R,Wrenn DS,Griffin GL,Senior RM

    更新日期:1989-05-02 00:00:00

  • Aluminum fluoride activation of bovine transducin induces two distinct conformational changes in the alpha subunit.

    abstract::We have used resonance energy transfer to read out the interactions of the alpha subunit of transducin (alpha T) with the transducin beta gamma subunit complex (beta gamma T) and to compare the rate of aluminum fluoride-induced alpha T activation, as reflected by the enhancement of the alpha T tryptophan fluorescence,...


    pub_type: 杂志文章


    authors: Mittal R,Cerione RA,Erickson JW

    更新日期:1994-08-23 00:00:00

  • Kinetics and fidelity of polymerization by DNA polymerase III from Sulfolobus solfataricus.

    abstract::We have biochemically and kinetically characterized the polymerase and exonuclease activities of the third B-family polymerase (Dpo3) from the hyperthermophilic Crenarchaeon, Sulfolobus solfataricus (Sso). We have established through mutagenesis that despite incomplete sequence conservation, the polymerase and exonucl...


    pub_type: 杂志文章


    authors: Bauer RJ,Begley MT,Trakselis MA

    更新日期:2012-03-06 00:00:00

  • Photoinactivation and photoaffinity labeling of tryptophan synthase alpha 2 beta 2 complex by the product analogue 6-azido-L-tryptophan.

    abstract::The photoaffinity reagent 6-azido-L-tryptophan was synthesized by chemical methods. It binds reversibly in the dark to the alpha 2 beta 2 complex of tryptophan synthase of Escherichia coli and forms a quinonoid intermediate with enzyme-bound pyridoxal phosphate (lambda max = 476 nm). The absorbance of this chromophore...


    pub_type: 杂志文章


    authors: Miles EW,Phillips RS

    更新日期:1985-08-13 00:00:00

  • Long-range interaction networks in the function and fidelity of poliovirus RNA-dependent RNA polymerase studied by nuclear magnetic resonance.

    abstract::The fidelity of the poliovirus RNA-dependent RNA polymerase (3D(pol)) plays a direct role in the genomic evolution and pathogenesis of the virus. A single site mutation (Gly64Ser) that is remote from the catalytic center results in a higher fidelity polymerase. NMR studies with [methyl-(13)C]methionine-labeled protein...


    pub_type: 杂志文章


    authors: Yang X,Welch JL,Arnold JJ,Boehr DD

    更新日期:2010-11-02 00:00:00

  • Ligand-induced differences in secondary structure of the Vibrio parahaemolyticus Na+/galactose cotransporter.

    abstract::A detailed structural study of the prokaryotic sodium/galactose transporter (vSGLT) from Vibrio parahaemolyticus using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy reveals stepwise increases in alpha-helicity upon binding of sodium and D-galactose. These increases in helicity correlat...


    pub_type: 杂志文章


    authors: le Coutre J,Turk E,Kaback HR,Wright EM

    更新日期:2002-06-25 00:00:00

  • Deletions in the interdomain hinge region of flavocytochrome b2: effects on intraprotein electron transfer.

    abstract::The two distinct domains of flavocytochrome b2 (L-lactate:cytochrome c oxidoreductase, EC are connected by a typical hinge peptide. To probe the importance of the structural integrity of the hinge region for efficient intraprotein electron transfer, three mutant enzymes have been constructed: H delta 3 [Sharp...


    pub_type: 杂志文章


    authors: Sharp RE,Chapman SK,Reid GA

    更新日期:1996-01-23 00:00:00

  • Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and thermodynamic binding mode examined in a 1.09 A structure.

    abstract::The structure of HIV protease (HIV Pr) bound to JE-2147 (also named AG1776 or KNI-764) is determined here to 1.09 A resolution. This highest-resolution structure for HIV Pr allows refinement of anisotropic displacement parameters (ADPs) for all atoms. Clustering based on the directional information in ADPs defines two...


    pub_type: 杂志文章


    authors: Reiling KK,Endres NF,Dauber DS,Craik CS,Stroud RM

    更新日期:2002-04-09 00:00:00

  • Progesterone-binding components of chick oviduct: analysis of receptor structure by limited proteolysis.

    abstract::An endogenous calcium-activated sulfhydryl protease in chick oviduct cytosol has been utilized to study the structure of the chick oviduct progesterone receptor subunits, progestophilins A (79 000 g/mol) and B (117 000 g/mol). The protease is not a normal component of the native progesterone receptor aggregate (6 and ...


    pub_type: 杂志文章


    authors: Vedeckis WV,Schrader WT,O'Malley BW

    更新日期:1980-01-22 00:00:00

  • Effect of pressure on deuterium isotope effects of yeast alcohol dehydrogenase: evidence for mechanical models of catalysis.

    abstract::Moderate pressure accelerates hydride transfer catalyzed by yeast alcohol dehydrogenase, indicative of a large negative volume of activation [Cho and Northrop (1999) Biochemistry 38, 7470-7475]. A comparison of the effects of pressure on the oxidation of normal versus dideuteriobenzyl alcohol generates a monophasic de...


    pub_type: 杂志文章


    authors: Northrop DB,Cho YK

    更新日期:2000-03-07 00:00:00

  • Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e.

    abstract::Five previously unknown hemorrhagic proteins, designated hemorrhagic toxins a,b,c,d, and e, were isolated from the venom of the western diamondback rattlesnake (Crotalus atrox). Molecular weights of hemorrhagic toxins a-e were determined to be 68 000, 24 000, 24 000, 24 000, and 25 700, respectively, by sodium dodecyl...


    pub_type: 杂志文章


    authors: Bjarnason JB,Tu AT

    更新日期:1978-08-08 00:00:00

  • Imaging and mapping heparin-binding sites on single fibronectin molecules with atomic force microscopy.

    abstract::Fibronectin is composed of multiple homologous repeats and contains many functional domains. Two major heparin-binding domains have previously been identified: the Hep I site near the amino terminus and the Hep II site near the carboxyl terminus. The Hep II site has been considered the high-affinity heparin-binding si...


    pub_type: 杂志文章


    authors: Lin H,Lal R,Clegg DO

    更新日期:2000-03-28 00:00:00

  • Treponema denticola PurE Is a bacterial AIR carboxylase.

    abstract::De novo purine biosynthesis proceeds by two divergent paths. In bacteria, yeasts, and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N(5)-carboxy-AIR (N(5)-CAIR) synthetase (PurK) and N(5)-CAIR mutase (class I PurE). In animals, the conversion of AIR to CAIR requires...


    pub_type: 杂志文章


    authors: Tranchimand S,Starks CM,Mathews II,Hockings SC,Kappock TJ

    更新日期:2011-05-31 00:00:00

  • Amino-terminal domain of TIF2 is involved in competing for corepressor binding to glucocorticoid and progesterone receptors.

    abstract::Both agonist- and antagonist-bound glucocorticoid receptors (GRs) and progesterone receptors (PRs) regulate gene transcription with the assistance of corepressors (NCoR and SMRT) and coactivators (TIF2/GRIP1, SRC1, and AIB1). Receptor binding of these cofactors is competitive and is considered to involve interactions ...


    pub_type: 杂志文章


    authors: Wang D,Wang Q,Awasthi S,Simons SS Jr

    更新日期:2007-07-10 00:00:00

  • Solution studies on the structure of bent DNA in the cAMP receptor protein-lac DNA complex.

    abstract::Cyclic AMP receptor protein is involved in the regulation of more than 20 genes. A step in the mechanism of activation of transcription is to induce a significant bending of the DNA upon complex formation between specific DNA and the protein. The induced DNA bending and a structure of the protein-DNA complex were stud...


    pub_type: 杂志文章


    authors: Heyduk T,Lee JC

    更新日期:1992-06-09 00:00:00

  • Nuclear Overhauser experiments at 500 MHz on the downfield proton spectra of 5S ribonucleic acid and its complex with ribosomal protein L25.

    abstract::The downfield (9-15 ppm) proton spectrum of Escherichia coli 5S RNA has been examined at 500 MHz by using nuclear Overhauser methods. The data confirm the existence of the terminal and procaryotic loop helices within the molecule [Fox, G. E., & Woese, C. R. (1975) Nature (London) 256, 505-506]. Very little stable, dou...


    pub_type: 杂志文章


    authors: Kime MJ,Moore PB

    更新日期:1983-05-24 00:00:00

  • The p73 DNA binding domain displays enhanced stability relative to its homologue, the tumor suppressor p53, and exhibits cooperative DNA binding.

    abstract::The p53 protein family is involved in the control of an intricate network of genes implicated in cell cycle, through to germ line integrity and development. Although the role of p53 is well-established, the intrinsic nature of its homologue p73 has yet to be fully elucidated. Here, the biochemical characterization and...


    pub_type: 杂志文章


    authors: Patel S,Bui TT,Drake AF,Fraternali F,Nikolova PV

    更新日期:2008-03-11 00:00:00

  • Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck.

    abstract::Herpesvirus saimiri codes for a tyrosine kinase interacting protein (Tip) that interacts with both the SH3 domain and the kinase domain of the T-cell-specific tyrosine kinase Lck via two separate motifs. The activation of Lck by Tip is considered as a key event in the transformation of human T-lymphocytes during herpe...


    pub_type: 杂志文章


    authors: Schweimer K,Hoffmann S,Bauer F,Friedrich U,Kardinal C,Feller SM,Biesinger B,Sticht H

    更新日期:2002-04-23 00:00:00

  • An Open Library of Human Kinase Domain Constructs for Automated Bacterial Expression.

    abstract::Kinases play a critical role in cellular signaling and are dysregulated in a number of diseases, such as cancer, diabetes, and neurodegeneration. Therapeutics targeting kinases currently account for roughly 50% of cancer drug discovery efforts. The ability to explore human kinase biochemistry and biophysics in the lab...


    pub_type: 杂志文章


    authors: Albanese SK,Parton DL,Işık M,Rodríguez-Laureano L,Hanson SM,Behr JM,Gradia S,Jeans C,Levinson NM,Seeliger MA,Chodera JD

    更新日期:2018-08-07 00:00:00

  • Structural characterization of folded and unfolded states of an SH3 domain in equilibrium in aqueous buffer.

    abstract::The isolated N-terminal Src homology 3 (SH3) domain of Drosophila drk exists in equilibrium between folded and unfolded states in aqueous buffer near neutral pH. Nuclear magnetic resonance spectra recorded on both states simultaneously exhibit an approximate 1:1 ratio of protein conformations. The folded form is simil...


    pub_type: 杂志文章


    authors: Zhang O,Forman-Kay JD

    更新日期:1995-05-23 00:00:00

  • Probing inhibitor-induced conformational changes along the interface between tissue factor and factor VIIa.

    abstract::Upon injury of a blood vessel, activated factor VII (FVIIa) forms a high-affinity complex with its allosteric regulator, tissue factor (TF), and initiates blood clotting. Active site-inhibited factor VIIa (FVIIai) binds to TF with even higher affinity. We compared the interactions of FVIIai and FVIIa with soluble TF (...


    pub_type: 杂志文章


    authors: Osterlund M,Owenius R,Carlsson K,Carlsson U,Persson E,Lindgren M,Freskgård PO,Svensson M

    更新日期:2001-08-07 00:00:00