当前位置： SCI文献检索 > BIOCHEMISTRY期刊下所有文献 > High-affinity insulin binding: insulin interacts with two receptor ligand binding sites.

High-affinity insulin binding: insulin interacts with two receptor ligand binding sites.

Abstract：

:The interaction of insulin with its receptor is complex. Kinetic and equilibrium binding studies suggest coexistence of high- and low-affinity binding sites or negative cooperativity. These phenomena and high-affinity interactions are dependent on the dimeric structure of the receptor. Structure-function studies of insulin analogs suggest insulin has two receptor binding sites, implying a bivalent interaction with the receptor. Alanine scanning studies of the secreted recombinant receptor implicate the L1 domain and a C-terminal peptide of the receptor alpha subunit as components of one ligand binding site. Functional studies suggest that the first and second type III fibronectin repeats of the receptor contain a second ligand binding site. We have used structure-directed alanine scanning mutagenesis to identify determinants in these domains involved in ligand interactions. cDNAs encoding alanine mutants of the holo-receptor were transiently expressed in 293 cells, and the binding properties of the expressed receptor were determined. Alanine mutations of Lys(484), Leu(552), Asp(591), Ile(602), Lys(616), Asp(620), and Pro(621) compromised affinities for insulin 2-5-fold. With the exception of Asp(620), none of these mutations compromised the affinity of the recombinant secreted receptor for insulin, indicating that the perturbation of the interaction is at the site of mutation and not an indirect effect on the interaction with the binding site of the secreted receptor. These residues thus form part of a novel ligand binding site of the insulin receptor. Complementation experiments demonstrate that insulin interacts in trans with both receptor binding sites to generate high-affinity interactions.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Whittaker L,Hao C,Fu W,Whittaker J

doi

10.1021/bi801693h

subject

Has Abstract

pub_date

2008-12-02 00:00:00

pages

12900-9

issue

48

eissn

0006-2960

issn

1520-4995

journal_volume

47

pub_type

杂志文章

相关文献

BIOCHEMISTRY文献大全
  • The application of 0.1 M quadrol to the microsequence of proteins and the sequence of tryptic peptides.

    abstract：:In an effort to extend automated Edman degradation to nanomole quantities of protein, the method of sequenator analysis described by Edman and Begg (Edman, P., and Begg, G. (1967), Eur. J. Biochem. 1, 80) was modified to permit long degradations in the absence of carrier proteins. By using an aqueous 0.1 M Quadrol pro...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00684a036

    authors： Brauer AW,Margolies MN,Haber E

    更新日期：1975-07-01 00:00:00

  • Structural and functional analysis of EcoRI DNA methyltransferase by proteolysis.

    abstract：:Native EcoRI DNA methyltransferase (Mtase, Mr 38,050) is proteolyzed by trypsin to generate an intermediate 36-kDa fragment (p36) followed by the formation of two polypeptides of Mr 23,000 and 13,000 (p23 and p13, respectively). Protein sequence analysis of the tryptic fragments indicates that p36 results from removal...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00225a030

    authors： Reich NO,Maegley KA,Shoemaker DD,Everett E

    更新日期：1991-03-19 00:00:00

  • Determination of the three-dimensional structure of the bifunctional alpha-amylase/trypsin inhibitor from ragi seeds by NMR spectroscopy.

    abstract：:The three-dimensional structure of the bifunctional alpha-amylase/trypsin inhibitor (RBI) from seeds of ragi (Eleusine coracana Gaertneri) has been determined in solution using multidimensional 1H and 15N NMR spectroscopy. The inhibitor consists of 122 amino acids, with 5 disulfide bridges, and belongs to the plant al...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00026a009

    authors： Strobl S,Mühlhahn P,Bernstein R,Wiltscheck R,Maskos K,Wunderlich M,Huber R,Glockshuber R,Holak TA

    更新日期：1995-07-04 00:00:00

  • (Z)-3-(fluoromethyl)phosphoenolpyruvate: synthesis and enzymatic studies.

    abstract：:(Z)-3-(Fluoromethyl)phosphoenolpyruvate has been synthesized in nine chemical steps from glyoxylic acid. The compound is stable at pH 3, but at pH 8 it decomposes within seconds to give 2-oxo-3-butenoate. When 3-(fluoromethyl)phosphoenolpyruvate is added to a solution of phosphoenolpyruvate carboxylase or pyruvate kin...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00404a039

    authors： Wirsching P,O'Leary MH

    更新日期：1988-02-23 00:00:00

  • Ligand binding and the catalytic reaction of cytochrome caa(3) from the thermophilic bacterium Rhodothermus marinus.

    abstract：:The ligand-binding dynamics and the reaction with O(2) of the fully (five-electron) reduced cytochrome caa(3) from the thermohalophilic bacterium Rhodothermus (R.) marinus were investigated. The enzyme is a proton pump which has all the residues of the proton-transfer pathways found in the mitochondrial-like enzymes c...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi010344h

    authors： Sigurdson H,Namslauer A,Pereira MM,Teixeira M,Brzezinski P

    更新日期：2001-09-04 00:00:00

  • Bleaching kinetics of artificial visual pigments with modifications near the ring-polyene chain connection.

    abstract：:Absorbance difference spectra were recorded at 20 degrees C from 30 ns to milliseconds after photolysis of lauryl maltoside suspensions of artificial visual pigments derived from 9-cis isomers of 5-ethylretinal, 8,16-methanoretinal (a 6-s-trans-bicyclic analogue), or 5-demethyl-8-methylretinal. In all three pigments, ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi011461f

    authors： Szundi I,de Lera AR,Pazos Y,Alvarez R,Oliana M,Sheves M,Lewis JW,Kliger DS

    更新日期：2002-02-12 00:00:00

  • Contribution of exogenous substrates to acetyl coenzyme A: measurement by 13C NMR under non-steady-state conditions.

    abstract：:A method is presented for the rapid determination of substrate selection in a manner that is not restricted to conditions of metabolic and isotopic steady state. Competition between several substrates can be assessed directly and continuously in a single experiment, allowing the effect of interventions to be studied. ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00481a002

    authors： Malloy CR,Thompson JR,Jeffrey FM,Sherry AD

    更新日期：1990-07-24 00:00:00

  • Protein arginine deiminase 4: evidence for a reverse protonation mechanism.

    abstract：:The presumed role of an overactive protein arginine deiminase 4 (PAD4) in the pathophysiology of rheumatoid arthritis (RA) suggests that PAD4 inhibitors could be used to treat an underlying cause of RA, potentially offering a mechanism to stop further disease progression. Thus, the development of such inhibitors is of...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi700095s

    authors： Knuckley B,Bhatia M,Thompson PR

    更新日期：2007-06-05 00:00:00

  • Chloroplast biogenesis: [4-vinyl] chlorophyllide a reductase is a divinyl chlorophyllide a-specific, NADPH-dependent enzyme.

    abstract：:Some properties of [4-vinyl] chlorophyllide a reductase are described. This enzyme converts divinyl chlorophyllide a to monovinyl chlorophyllide a. The latter is the immediate precursor of monovinyl chlorophyll a, the main chlorophyll in green plants. [4-Vinyl] chlorophyllide a reductase plays an important role in day...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00151a011

    authors： Parham R,Rebeiz CA

    更新日期：1992-09-15 00:00:00

  • Protection of satellite tobacco necrosis virus ribonucleic acid by wheat germ 40S and 80S ribosomes.

    abstract：:Wheat germ ribosomes combine with the AUG codon at positions 30-32 from the 5' terminus of in vitro radioiodinated satellite tobacco necrosis virus (STNV) ribonucleic acid (RNA) to form initiation complexes that protect specific regions of the RNA from attack by ribonucleases. Wheat gern 80S ribosomes convey partial p...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00551a044

    authors： Browning KS,Leung DW,Clark JM Jr

    更新日期：1980-05-13 00:00:00

  • Dynamics of activation of lecithin:cholesterol acyltransferase by apolipoprotein A-I.

    abstract：:The product of transesterification of phospholipid acyl chains and unesterified cholesterol (UC) by the enzyme lecithin:cholesterol acyltransferase (LCAT) is cholesteryl ester (CE). Activation of LCAT by apolipoprotein (apo) A-I on nascent (discoidal) high-density lipoproteins (HDL) is essential for formation of matur...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi901242k

    authors： Jones MK,Catte A,Li L,Segrest JP

    更新日期：2009-12-01 00:00:00

  • Raman spectroscopy of synthetic antimicrobial frog peptides magainin 2a and PGLa.

    abstract：:Magainin and PGLa are 23- and 21-residue peptides isolated from the skin of the African clawed frog Xenopus laevis. They protect the frog from infection and exhibit a broad-spectrum antimicrobial activity in vitro. The mechanism of this activity involves the interaction of magainin with microbial membranes. We have me...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00470a031

    authors： Williams RW,Starman R,Taylor KM,Gable K,Beeler T,Zasloff M,Covell D

    更新日期：1990-05-08 00:00:00

  • A 50 KDa protein modulates guanine nucleotide binding of transglutaminase II.

    abstract：:Regulation of cellular response is an important mechanism for controlling cellular functions. The transmembrane signaling of the hormone receptors is regulated by GTP-binding proteins (GTPases) and their associated proteins. Our previous studies demonstrated that the bifunctional GTP-binding protein, G alpha h (transg...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi9522965

    authors： Baek KJ,Das T,Gray CD,Desai S,Hwang KC,Gacchui R,Ludwig M,Im MJ

    更新日期：1996-02-27 00:00:00

  • 19F NMR studies of the D-galactose chemosensory receptor. 2. Ca(II) binding yields a local structural change.

    abstract：:The Escherichia coli D-galactose and D-glucose receptor possesses a Ca(II)-binding site closely related in structure and metal-binding characteristics to the eukaryotic EF-hand sites. Only the structure of the Ca(II)-occupied site is known. To investigate the structural change triggered by Ca(II) and Sr(II) binding, w...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00231a022

    authors： Luck LA,Falke JJ

    更新日期：1991-04-30 00:00:00

  • Assembly of microtubules from tubulin bearing the nonhydrolyzable guanosine triphosphate analogue GMPPCP [guanylyl 5'-(beta, gamma-methylenediphosphonate)]: variability of growth rates and the hydrolysis of GTP.

    abstract：:The growth and shortening of microtubules in guanosine triphosphate-(GTP-) mediated dynamic instability has previously been observed to occur at rates which are remarkably variable (Gildersleeve et al., 1992, Chrétien et al., 1995). Neighboring microtubules observed simultaneously can grow or shorten at different rate...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi961070e

    authors： Dye RB,Williams RC Jr

    更新日期：1996-11-12 00:00:00

  • Aggregation behaviour and Zn2+ binding properties of secretin.

    abstract：:Dynamic light scattering measurements were carried out on secretin in aqueous solution (2 mM; pH 5.0). The results indicated that the molecule exists as a fairly compact hexamer under these solution conditions. Secondary structural properties of the secretin hexameric complex were evaluated using CD and NMR spectrosco...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi980701x

    authors： Carpenter KA,Schiller PW

    更新日期：1998-12-01 00:00:00

  • Mechanism of the oxidation reaction of deoxyhemoglobin as studied by isolation of the intermediates suggests tertiary structure dependent cooperativity.

    abstract：:The intermediates in the oxidation of deoxyhemoglobin by ferricyanide in 0.1 M KCl, at 20 degrees C and three pH values, were studied by cryogenic techniques. Data analysis was carried out according to a simple four rate constant model, ignoring the functional heterogeneity of the subunits, to simulate the time course...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00070a035

    authors： Perrella M,Shrager RI,Ripamonti M,Manfredi G,Berger RL,Rossi-Bernardi L

    更新日期：1993-05-18 00:00:00

  • Roles of aquaporin-4 isoforms and amino acids in square array assembly.

    abstract：:Aquaporin-4 (AQP4) is a water channel found at high concentrations around blood vessels in the brain and is organized into elaborate assemblies called square arrays. The natural functions of AQP4 and the square arrays remain unknown, but under pathophysiological conditions, AQP4 has been shown to influence brain edema...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi802231q

    authors： Strand L,Moe SE,Solbu TT,Vaadal M,Holen T

    更新日期：2009-06-30 00:00:00

  • Modification of Escherichia coli ribosomes with the fluorescent reagent N-[[(iodoacetyl)amino]ethyl]-5-naphthylamine-1-sulfonic acid. Identification of derivatized L31' and studies on its intraribosomal properties.

    abstract：:N-[[(Iodoacetyl)amino]ethyl]-5-naphthylamine-1-sulfonic acid (IAEDANS) is a fluorescent reagent which reacts covalently with the free thiol groups of proteins. When the reagent is reacted with the Escherichia coli ribosome under mild conditions, gel electrophoresis shows modification of predominantly two proteins, S18...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00346a042

    authors： Hanas JS,Simpson MV

    更新日期：1985-12-03 00:00:00

  • Biochemical and Functional Evaluation of the Intramolecular Disulfide Bonds in the Zinc-Chelating Antimicrobial Protein Human S100A7 (Psoriasin).

    abstract：:Human S100A7 (psoriasin) is a metal-chelating protein expressed by epithelial cells. It is a 22-kDa homodimer with two EF-hand domains per subunit and two transition-metal-binding His3Asp sites at the dimer interface. Each subunit contains two cysteine residues that can exist as free thiols (S100A7red) or as an intram...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.7b00781

    authors： Cunden LS,Brophy MB,Rodriguez GE,Flaxman HA,Nolan EM

    更新日期：2017-10-31 00:00:00

  • Role of structural and energetic factors in regulating repair of a bulky DNA lesion with different opposite partner bases.

    abstract：:Extensive molecular modeling with molecular dynamics simulations and van der Waals energy analyses were used to elucidate the striking finding that a mutagenic benzo[a]pyrene-derived DNA lesion, the base-displaced intercalated 10R-(+)-cis-anti-B[a]P-N(2)-dG (G*), manifests large differences in nucleotide excision repa...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi4009177

    authors： Mu H,Kropachev K,Chen Y,Zhang H,Cai Y,Geacintov NE,Broyde S

    更新日期：2013-08-20 00:00:00

  • NSC 622124 inhibits human Eg5 and other kinesins via interaction with the conserved microtubule-binding site.

    abstract：:Kinesin-5 proteins are essential for formation of a bipolar mitotic spindle in most and, perhaps all, eukaryotic cells. Several Kinesin-5 proteins, notably the human version, HsEg5, are targets of a constantly expanding group of small-molecule inhibitors, which hold promise both as tools for probing mechanochemical tr...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi801291q

    authors： Learman SS,Kim CD,Stevens NS,Kim S,Wojcik EJ,Walker RA

    更新日期：2009-03-03 00:00:00

  • Study of the conformational transition of A beta(1-42) using D-amino acid replacement analogues.

    abstract：:A critical event in Alzheimer's disease is the transition of Abeta peptides from their soluble forms into disease-associated beta-sheet-rich conformers. Structural analysis of a complete D-amino acid replacement set of Abeta(1-42) enabled us to localize in the full-length 42-mer peptide the region responsible for the ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi002005e

    authors： Janek K,Rothemund S,Gast K,Beyermann M,Zipper J,Fabian H,Bienert M,Krause E

    更新日期：2001-05-08 00:00:00

  • Mutation of Arg-166 of alkaline phosphatase alters the thio effect but not the transition state for phosphoryl transfer. Implications for the interpretation of thio effects in reactions of phosphatases.

    abstract：:It has been suggested that the mechanism of alkaline phosphatase (AP) is associative, or triester-like, because phosphorothioate monoesters are hydrolyzed by AP approximately 10(2)-fold slower than phosphate monoesters. This "thio effect" is similar to that observed for the nonenzymatic hydrolysis of phosphate trieste...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi000899x

    authors： Holtz KM,Catrina IE,Hengge AC,Kantrowitz ER

    更新日期：2000-08-08 00:00:00

  • Biostructural chemistry of magnesium ion: characterization of the weak binding sites on tRNA(Phe)(yeast). Implications for conformational change and activity.

    abstract：:The thermodynamics and kinetics of magnesium binding to tRNA(Phe)(yeast) have been studied directly by 25Mg NMR. In 0.17 M Na+(aq), tRNA(Phe) exists in its native conformation and the number of strong binding sites (Ka greater than or equal to 10(4)) was estimated to be 3-4 by titration experiments, in agreement with ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00477a021

    authors： Reid SS,Cowan JA

    更新日期：1990-06-26 00:00:00

  • tRNA 3' processing in plants: nuclear and mitochondrial activities differ.

    abstract：:The nuclear tRNA 3' processing activity from wheat has been characterized and partially purified. Several characteristics of the wheat nuclear 3' processing enzyme now allow this activity to be distinguished from its mitochondrial counterpart. The nuclear enzyme is an endonuclease, which we termed nuclear RNase Z. The...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi992253e

    authors： Mayer M,Schiffer S,Marchfelder A

    更新日期：2000-02-29 00:00:00

  • CoCl(2) induces apoptosis via the 18 kDa translocator protein in U118MG human glioblastoma cells.

    abstract：:The 18 kDa translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, has been reported to be closely associated with the mitochondrial permeability transition pore (MPTP). TSPO is believed to exert pro-apoptotic functions via modulation of MPTP opening. Cobalt chloride (CoCl(2)), whic...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi900064t

    authors： Zeno S,Zaaroor M,Leschiner S,Veenman L,Gavish M

    更新日期：2009-06-02 00:00:00

  • Phospholipids stabilize the interaction between the alpha and beta subunits of the solubilized receptor for immunoglobulin E.

    abstract：:The cell-surface component (alpha) which binds monomeric immunoglobulin E with high affinity is associated with a second polypeptide (beta) in the plasma membrane. The latter component tends to dissociate during purification of the alpha chain from detergent extracts of cells, even at neutral pHs and physiological ion...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00269a047

    authors： Rivnay B,Wank SA,Poy G,Metzger H

    更新日期：1982-12-21 00:00:00

  • Calorimetric studies of the binding of ferric ions to human serum transferrin.

    abstract：:The binding of ferric ions, chelated with nitrilotriacetate, to human serum transferrin (hTF) has been studied using ultrasensitive titration calorimetry. Studies were done in both the presence and the absence of the synergistic bicarbonate anion. It was found that the C-site of hTF is capable of weakly binding bicarb...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00087a019

    authors： Lin LN,Mason AB,Woodworth RC,Brandts JF

    更新日期：1993-09-14 00:00:00

  • NMR studies of the phosphotransfer domain of the histidine kinase CheA from Escherichia coli: assignments, secondary structure, general fold, and backbone dynamics.

    abstract：:Multidimensional heteronuclear NMR techniques were applied to study the phosphotransfer domain, residues 1-134, of the histidine kinase CheA, from Escherichia coli, which contains the site of autophosphorylation, His48. Assignments of the backbone amide groups and side chain protons are nearly complete. Our studies sh...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00042a018

    authors： Zhou H,Lowry DF,Swanson RV,Simon MI,Dahlquist FW

    更新日期：1995-10-24 00:00:00