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












  • Biochemical characterization and crystallographic structure of an Escherichia coli protein from the phosphotriesterase gene family.

    abstract::Phosphotriesterase homology protein (PHP) is a member of a recently discovered family of proteins related to phosphotriesterase, a hydrolytic, bacterial enzyme with an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates, which are common constituents of chemical warfare agent...


    pub_type: 杂志文章


    authors: Buchbinder JL,Stephenson RC,Dresser MJ,Pitera JW,Scanlan TS,Fletterick RJ

    更新日期:1998-04-14 00:00:00

  • Ethanol-perturbed amyloidogenic self-assembly of insulin: looking for origins of amyloid strains.

    abstract::A model cosolvent, ethanol, has profound and diversified effects on the amyloidogenic self-assembly of insulin, yielding spectroscopically and morphologically distinguishable forms of beta-aggregates. The alcohol reduces hydrodynamic radii of insulin molecules, decreases enthalpic costs associated with aggregation-pro...


    pub_type: 杂志文章


    authors: Dzwolak W,Grudzielanek S,Smirnovas V,Ravindra R,Nicolini C,Jansen R,Loksztejn A,Porowski S,Winter R

    更新日期:2005-06-28 00:00:00

  • Interaction between the Rev1 C-Terminal Domain and the PolD3 Subunit of Polζ Suggests a Mechanism of Polymerase Exchange upon Rev1/Polζ-Dependent Translesion Synthesis.

    abstract::Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first ste...


    pub_type: 杂志文章


    authors: Pustovalova Y,Magalhães MT,D'Souza S,Rizzo AA,Korza G,Walker GC,Korzhnev DM

    更新日期:2016-04-05 00:00:00

  • Redundancy of mammalian proteasome beta subunit function during endoplasmic reticulum associated degradation.

    abstract::Misfolded proteins in the endoplasmic reticulum (ER) are degraded by N-terminal threonine proteases within the 26S proteasome. Each protease is formed by an activated beta subunit, beta5/X, beta1/Y, or beta2/Z, that exhibits chymotrypsin-like, peptidylglutamyl-peptide hydrolyzing, or trypsin-like activity, respectivel...


    pub_type: 杂志文章


    authors: Oberdorf J,Carlson EJ,Skach WR

    更新日期:2001-11-06 00:00:00

  • Modular mutagenesis of exons 1, 2, and 8 of a glutathione S-transferase from the mu class. Mechanistic and structural consequences for chimeras of isoenzyme 3-3.

    abstract::Exons 1 and 2 and exon 8 of the mu class GSH transferases from rat encode sequence-variable regions 1 and 4 of mu class isoenzymes, respectively. These two of four variable regions are located at the N- and C-termini of this isoenzyme class and impinge on the active site. In order to assess the influence of these vari...


    pub_type: 杂志文章


    authors: Zhang P,Liu S,Shan SO,Ji X,Gilliland GL,Armstrong RN

    更新日期:1992-10-27 00:00:00

  • Characterization of a novel dUTP-dependent activity of CTP synthetase from Saccharomyces cerevisiae.

    abstract::CTP synthetase [EC, UTP:ammonia ligase (ADP-forming)] from the yeast Saccharomyces cerevisiae catalyzes the ATP-dependent transfer of the amide nitrogen from glutamine to the C-4 position of UTP to form CTP. In this work, we demonstrated that CTP synthetase utilized dUTP as a substrate to synthesize dCTP. The ...


    pub_type: 杂志文章


    authors: Pappas A,Park TS,Carman GM

    更新日期:1999-12-14 00:00:00

  • Inhibition of protein interactions with the beta 2 sliding clamp of Escherichia coli DNA polymerase III by peptides from beta 2-binding proteins.

    abstract::The sliding clamp of the Escherichia coli replisome is now understood to interact with many proteins involved in DNA synthesis and repair. A universal interaction motif is proposed to be one mechanism by which those proteins bind the E. coli sliding clamp, a homodimer of the beta subunit, at a single site on the dimer...


    pub_type: 杂志文章


    authors: Wijffels G,Dalrymple BP,Prosselkov P,Kongsuwan K,Epa VC,Lilley PE,Jergic S,Buchardt J,Brown SE,Alewood PF,Jennings PA,Dixon NE

    更新日期:2004-05-18 00:00:00

  • Physical and conformational properties of synthetic idealized signal sequences parallel their biological function.

    abstract::Transported proteins often contain an extension sequence called the signal peptide. The alkaline phosphatase (PhoA) signal sequence represents a typical signal peptide for comparison to idealized sequences both in vivo and in vitro. We have designed a series of idealized signal sequences which vary in amino terminal c...


    pub_type: 杂志文章


    authors: Izard JW,Doughty MB,Kendall DA

    更新日期:1995-08-08 00:00:00

  • Cytochrome P-450 inactivation by 3-alkylsydnones. Mechanistic implications of N-alkyl and N-alkenyl heme adduct formation.

    abstract::Incubation of 3-(2-phenylethyl)-4-methylsydnone (PMS) with liver microsomes from phenobarbital-pretreated rats or with reconstituted cytochrome P-450b results in loss of the enzyme chromophore. Chromophore loss is NADPH-dependent even though the sydnone decomposes by an oxygen- but not enzyme-dependent process to give...


    pub_type: 杂志文章


    authors: Grab LA,Swanson BA,Ortiz de Montellano PR

    更新日期:1988-06-28 00:00:00

  • Specific interaction of wild-type and truncated mouse N-methylpurine-DNA glycosylase with ethenoadenine-containing DNA.

    abstract::N-Methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, is responsible for the removal of a wide variety of alkylated base lesions in DNA, e.g., N-alkylpurines and cyclic ethenoadducts of adenine, guanine, and cytosine. These lesions, some of which are mutagenic and toxic, are generated endogenously or b...


    pub_type: 杂志文章


    authors: Roy R,Biswas T,Hazra TK,Roy G,Grabowski DT,Izumi T,Srinivasan G,Mitra S

    更新日期:1998-01-13 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

  • Solvent isotope effects on the onset of inhibition of porcine pepsin by pepstatin.

    abstract::Pepstatin is a slow and tight-binding inhibitor of pepsin. Preincubating enzyme and inhibitor in H2O and in D2O in the absence of substrate generates an inverse solvent isotope effect of Dk = 0.69 +/- 0.06 on the apparent first-order rate constant for the decay in enzymatic activity. Proton inventory analysis of the i...


    pub_type: 杂志文章


    authors: Cho YK,Rebholz KL,Northrop DB

    更新日期:1994-08-16 00:00:00

  • Exchange of histidine spacing between Sp1 and GLI zinc fingers: distinct effect of histidine spacing-linker region on DNA binding.

    abstract::In the DNA recognition mode of C(2)H(2)-type zinc fingers, the finger-finger connection region, consisting of the histidine spacing (HX(3-5)H) and linker, would be important for determining the orientation of the zinc finger domains. To clarify the influence of spacing between two ligand histidines in the DNA binding,...


    pub_type: 杂志文章


    authors: Shiraishi Y,Imanishi M,Sugiura Y

    更新日期:2004-05-25 00:00:00

  • Irreversible inhibition of serine proteases by peptide derivatives of (alpha-aminoalkyl)phosphonate diphenyl esters.

    abstract::Peptidyl derivatives of diphenyl (alpha-aminoalkyl)phosphonates have been synthesized and are effective and specific inhibitors of serine proteases at low concentrations. Z-PheP(OPh)2 irreversibly reacts with chymotrypsin (kobsd/[I] = 1200 M-1 s-1) and does not react with two elastases. The best inhibitor for most chy...


    pub_type: 杂志文章


    authors: Oleksyszyn J,Powers JC

    更新日期:1991-01-15 00:00:00

  • Nuclear magnetic resonance and neutron diffraction studies of the complex of ribonuclease A with uridine vanadate, a transition-state analogue.

    abstract::The complex of ribonuclease A (RNase A) with uridine vanadate (U-V), a transition-state analogue, has been studied with 51V and proton NMR spectroscopy in solution and by neutron diffraction in the crystalline state. Upon the addition of aliquots of U-V at pH 6.6, the C epsilon-H resonances of the two active-site hist...


    pub_type: 杂志文章


    authors: Borah B,Chen CW,Egan W,Miller M,Wlodawer A,Cohen JS

    更新日期:1985-04-09 00:00:00

  • Characterization of a protein-generated O₂ binding pocket in PqqC, a cofactorless oxidase catalyzing the final step in PQQ production.

    abstract::PQQ is an exogenous, tricyclic, quino-cofactor for a number of bacterial dehydrogenases. The final step of PQQ formation is catalyzed by PqqC, a cofactorless oxidase. This study focuses on the activation of molecular oxygen in an enzyme active site without metal or cofactor and has identified a specific oxygen binding...


    pub_type: 杂志文章


    authors: RoseFigura JM,Puehringer S,Schwarzenbacher R,Toyama H,Klinman JP

    更新日期:2011-03-08 00:00:00

  • Probing Structural Dynamics and Topology of the KCNE1 Membrane Protein in Lipid Bilayers via Site-Directed Spin Labeling and Electron Paramagnetic Resonance Spectroscopy.

    abstract::KCNE1 is a single transmembrane protein that modulates the function of voltage-gated potassium channels, including KCNQ1. Hereditary mutations in the genes encoding either protein can result in diseases such as congenital deafness, long QT syndrome, ventricular tachyarrhythmia, syncope, and sudden cardiac death. Despi...


    pub_type: 杂志文章


    authors: Sahu ID,Craig AF,Dunagan MM,Troxel KR,Zhang R,Meiberg AG,Harmon CN,McCarrick RM,Kroncke BM,Sanders CR,Lorigan GA

    更新日期:2015-10-20 00:00:00

  • Conformational and aggregational properties of the gene 9 minor coat protein of bacteriophage M13 in membrane-mimicking systems.

    abstract::The membrane-bound state of the gene 9 minor coat protein of bacteriophage M13 was studied in various membrane-mimicking systems, including organic solvents, detergent micelles, and phospholipid bilayers. For this purpose we determined the conformational and aggregational properties of the chemically synthesized prote...


    pub_type: 杂志文章


    authors: Houbiers MC,Spruijt RB,Wolfs CJ,Hemminga MA

    更新日期:1999-01-19 00:00:00

  • Phenotypically selected mutations in myosin's actin binding domain demonstrate intermolecular contacts important for motor function.

    abstract::Here, we biochemically characterize Dictyostelium myosin II mutants that were previously phenotypically selected following random mutagenesis and shown to lie in the actin binding domain [Patterson, B., & Spudich, J. A. (1996) Genetics 143, 801-810]. We show that the conditional loss of myosin-dependent activity in vi...


    pub_type: 杂志文章


    authors: Giese KC,Spudich JA

    更新日期:1997-07-15 00:00:00

  • Subunit disassembly and unfolding kinetics of hemoglobin studied by time-resolved electrospray mass spectrometry.

    abstract::We report the use of electrospray ionization (ESI) mass spectrometry (MS) in conjunction with online rapid mixing to monitor the kinetics of acid-induced ferrihemoglobin denaturation. Under equilibrium conditions, the hemoglobin mass spectrum is dominated by the intact heterotetramer. Dimeric and monomeric species are...


    pub_type: 杂志文章


    authors: Simmons DA,Wilson DJ,Lajoie GA,Doherty-Kirby A,Konermann L

    更新日期:2004-11-23 00:00:00

  • Structure of the ternary complex formed by a chemotaxis receptor signaling domain, the CheA histidine kinase, and the coupling protein CheW as determined by pulsed dipolar ESR spectroscopy.

    abstract::The signaling apparatus that controls bacterial chemotaxis is composed of a core complex containing chemoreceptors, the histidine autokinase CheA, and the coupling protein CheW. Site-specific spin labeling and pulsed dipolar ESR spectroscopy (PDS) have been applied to investigate the structure of a soluble ternary com...


    pub_type: 杂志文章


    authors: Bhatnagar J,Borbat PP,Pollard AM,Bilwes AM,Freed JH,Crane BR

    更新日期:2010-05-11 00:00:00

  • Hydrogen exchange kinetics changes upon formation of the soybean trypsin inhibitor-trypsin complex.

    abstract::The hydrogen exchange kinetics of the complex of trypsin-soybean trypsin inhibitor (Kunitz) have been compared to the calculated sum of the exchange kinetics for the inhibitor and trypsin measured separately. The exchange rates observed for the complex are substantially less than the sum of the exchange rates in the t...


    pub_type: 杂志文章


    authors: Woodward CK,Ellis LM

    更新日期:1975-07-29 00:00:00

  • Aggregation of Alzheimer's amyloid β-peptide in biological membranes: a molecular dynamics study.

    abstract::Numerous studies have concluded that the interaction of the amyloid β-peptide (Aβ) and cellular membranes contributes to the toxicity and cell death observed in the progression of Alzheimer's disease. Aggregated Aβ species disrupt membranes, leading to physical instability and ion leakage. Further, the presence of Aβ ...


    pub_type: 杂志文章


    authors: Lemkul JA,Bevan DR

    更新日期:2013-07-23 00:00:00

  • Studies with recombinant Saccharomyces cerevisiae CaaX prenyl protease Rce1p.

    abstract::Eukaryotic proteins with carboxyl-terminal CaaX motifs undergo three post-translational processing reactions-protein prenylation, endoproteolysis, and carboxymethylation. Two genes in yeast encoding CaaX endoproteases, AFC1 and RCE1, have been identified. Rce1p is solely responsible for proteolysis of yeast Ras protei...


    pub_type: 杂志文章


    authors: Dolence JM,Steward LE,Dolence EK,Wong DH,Poulter CD

    更新日期:2000-04-11 00:00:00

  • Tight hydrophobic contacts with the SecB chaperone prevent folding of substrate proteins.

    abstract::The molecular chaperone SecB binds to hydrophobic sections of unfolded secretory proteins and thereby prevents their premature folding prior to secretion by the translocase of Escherichia coli. Here, we have investigated the effect of the single-residue mutation of leucine 42 to arginine (L42R) centrally positioned in...


    pub_type: 杂志文章


    authors: Bechtluft P,Kedrov A,Slotboom DJ,Nouwen N,Tans SJ,Driessen AJ

    更新日期:2010-03-23 00:00:00

  • SH2 domains mediate the sequential phosphorylation of HS1 protein by p72syk and Src-related protein tyrosine kinases.

    abstract::The protein tyrosine kinase p72syk readily phosphorylates hematopoietic linkage cell-specific protein p50/HS1 with high stoichiometry (up to 4 mol of Pi/mol of protein) and favorable kinetic constants (Km 77 nM, kcat 0.37 s-1), at sites that display the motif that is specifically recognized by the HS2 domains of Src t...


    pub_type: 杂志文章


    authors: Ruzzene M,Brunati AM,Marin O,Donella-Deana A,Pinna LA

    更新日期:1996-04-23 00:00:00

  • Catalytic mechanism of enzymes: preorganization, short strong hydrogen bond, and charge buffering.

    abstract::During the past decade, there has been much debate about the enormous catalytic rate enhancement observed in enzymatic reactions involving carbanion intermediates. Our recent theoretical study has demonstrated the importance of the short strong hydrogen bond (SSHB) in the enzymatic reactions. Nevertheless, other recen...


    pub_type: 杂志文章


    authors: Kim KS,Kim D,Lee JY,Tarakeshwar P,Oh KS

    更新日期:2002-04-23 00:00:00

  • Stereochemistry of phospho group transfer catalyzed by a mutant alkaline phosphatase.

    abstract::The stereochemical course of the phospho group transfer catalyzed by mutant (S102C) alkaline phosphatase from Escherichia coli was investigated by using 31P nuclear magnetic resonance spectroscopy. Transphosphorylation from 4-nitrophenyl (Rp)-[16O, 17O, 18O]phosphate to (S)-propane-1,2-diol occurs with overall retenti...


    pub_type: 杂志文章


    authors: Butler-Ransohoff JE,Kendall DA,Freeman S,Knowles JR,Kaiser ET

    更新日期:1988-06-28 00:00:00

  • Effects of putative catalytic base mutation E211Q on ABCG2-mediated methotrexate transport.

    abstract::ABCG2 is a half-ATP binding cassette (ABC) drug transporter that consists of a nucleotide binding domain (NBD) followed by a transmembrane domain. This half-ABC transporter is thought to form a homodimer in the plasma membrane where it transports anticancer drugs across the biological membranes in an ATP-dependent man...


    pub_type: 杂志文章


    authors: Hou YX,Li CZ,Palaniyandi K,Magtibay PM,Homolya L,Sarkadi B,Chang XB

    更新日期:2009-09-29 00:00:00

  • HlyC, the internal protein acyltransferase that activates hemolysin toxin: the role of conserved tyrosine and arginine residues in enzymatic activity as probed by chemical modification and site-directed mutagenesis.

    abstract::Internal fatty acylation of proteins is a recognized means of modifying biological behavior. Escherichia coli hemolysin A (HlyA), a toxic protein, is transcribed as a nontoxic protein and made toxic by internal acylation of two lysine residue epsilon-amino groups; HlyC catalyzes the acyl transfer from acyl-acyl carrie...


    pub_type: 杂志文章


    authors: Trent MS,Worsham LM,Ernst-Fonberg ML

    更新日期:1999-07-06 00:00:00