Phosphatidylinositol 4,5-bisphosphate alters synaptotagmin 1 membrane docking and drives opposing bilayers closer together.


:Synaptotagmin 1 (syt1) is a synaptic vesicle-anchored membrane protein that acts as the calcium sensor for the synchronous component of neuronal exocytosis. Using site-directed spin labeling, the position and membrane interactions of a fragment of syt1 containing its two C2 domains (syt1C2AB) were assessed in bilayers containing phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol 4,5-bisphosphate (PIP(2)). Addition of 1 mol % PIP(2) to a lipid mixture of PC and PS results in a deeper membrane penetration of the C2A domain and alters the orientation of the C2B domain so that the polybasic face of C2B comes into the proximity of the bilayer interface. The C2B domain is found to contact the membrane interface in two regions, the Ca(2+)-binding loops and a region opposite the Ca(2+)-binding loops. This suggests that syt1C2AB is configured to bridge two bilayers and is consistent with a model generated previously for syt1C2AB bound to membranes of PC and PS. Point-to-plane depth restraints, obtained by progressive power saturation, and interdomain distance restraints, obtained by double electron-electron resonance, were obtained in the presence of PIP(2) and used in a simulated annealing routine to dock syt1C2AB to two membrane interfaces. The results yield an average structure different from what is found in the absence of PIP(2) and indicate that bilayer-bilayer spacing is decreased in the presence of PIP(2). The results indicate that PIP(2), which is necessary for bilayer fusion, alters C2 domain orientation, enhances syt1-membrane electrostatic interactions, and acts to drive vesicle and cytoplasmic membrane surfaces closer together.






Kuo W,Herrick DZ,Cafiso DS




Has Abstract


2011-04-05 00:00:00












  • Groups with polar characteristics can locate at both shallow and deep locations in membranes: the behavior of dansyl and related probes.

    abstract::To understand the relationship between the chemical structure of polar molecules and their membrane location, the behavior of dansyl (dimethylaminonaphthalenesulfonyl) and related polar fluorescent probes was examined. The depth of these probes in lipid bilayers was determined by parallax analysis of fluorescence quen...


    pub_type: 杂志文章


    authors: Asuncion-Punzalan E,Kachel K,London E

    更新日期:1998-03-31 00:00:00

  • Protease Inhibition Mechanism of Camelid-like Synthetic Human Antibodies.

    abstract::Macromolecular protease inhibitors and camelid single-domain antibodies achieve their enzymic inhibition functions often through protruded structures that directly interact with catalytic centers of targeted proteases. Inspired by this phenomenon, we constructed synthetic human antibody libraries encoding long CDR-H3s...


    pub_type: 杂志文章


    authors: Nam DH,Lee KB,Kruchowy E,Pham H,Ge X

    更新日期:2020-10-13 00:00:00

  • Purification and characterization of a tissue plasminogen activator-inhibitor complex from human umbilical vein endothelial cell conditioned medium.

    abstract::Tissue plasminogen activator-inhibitor complexes were purified from the conditioned medium of human umbilical vein endothelial cells by affinity chromatography followed by gel filtration. It was found that a single complex was isolated which can exist in two distinct interconvertible conformations. These may be separa...


    pub_type: 杂志文章


    authors: Sanzo MA,Marasa JC,Wittwer AJ,Siegel NR,Harakas NK,Feder J

    更新日期:1987-11-17 00:00:00

  • Peptidomics of prolyl endopeptidase in the central nervous system.

    abstract::Prolyl endopeptidase (Prep) is a member of the prolyl peptidase family and is of interest because of its unique biochemistry and connections to cognitive function. Using an unbiased mass spectrometry (MS)-based peptidomics platform, we identified Prep-regulated peptides in the central nervous system (CNS) of mice by m...


    pub_type: 杂志文章


    authors: Nolte WM,Tagore DM,Lane WS,Saghatelian A

    更新日期:2009-12-22 00:00:00

  • Circular dichroism spectroscopy of the intermediates that precede the rate-limiting step of the refolding pathway of bovine pancreatic trypsin inhibitor. Relationship of conformation and the refolding pathway.

    abstract::Circular dichroism spectra of the partially folded trapped intermediates were measured in order to aid in the elucidation of the conformational forces which determine a nonrandom, nonsequential pathway of disulfide bond formation upon refolding of bovine pancreatic trypsin inhibitor. Whatever conformation was responsi...


    pub_type: 杂志文章


    authors: Kosen PA,Creighton TE,Blout ER

    更新日期:1983-05-10 00:00:00

  • Investigation of quercetin binding sites on chloroplast coupling factor 1.

    abstract::The quercetin binding sites on spinach chloroplast coupling factor 1 (CF1) have been investigated using direct and competitive binding, stopped-flow, temperature-jump, and fluorescence resonance energy transfer measurements. It was found that 8-anilino-1-naphthalensulfonic acid (ANS) competes with quercetin binding at...


    pub_type: 杂志文章


    authors: Cantley LC Jr,Hammes GG

    更新日期:1976-01-13 00:00:00

  • Assembly of a [2Fe-2S]2+ cluster in a molecular variant of Clostridium pasteurianum rubredoxin.

    abstract::The rubredoxin from Clostridium pasteurianum contains a single iron atom bound to the polypeptide chain by cysteines 6, 9, 39, and 42. The C42A variant of this protein has been prepared by site-directed mutagenesis and heterologous expression of the gene in Escherichia coli. The mutated protein was found to contain an...


    pub_type: 杂志文章


    authors: Meyer J,Gagnon J,Gaillard J,Lutz M,Achim C,Münck E,Pétillot Y,Colangelo CM,Scott RA

    更新日期:1997-10-28 00:00:00

  • Involvement of carboxy-terminal amino acids in secretion of human lysosomal protease cathepsin L.

    abstract::Cathepsin L, a lysosomal cysteine protease, is overexpressed and secreted by malignantly transformed cells. However, the reason for secretion of this man 6-phosphate-containing lysosomal protease into the extracellular medium is not clear. We wished to determine whether there is a region within the primary sequence of...


    pub_type: 杂志文章


    authors: Chauhan SS,Ray D,Kane SE,Willingham MC,Gottesman MM

    更新日期:1998-06-09 00:00:00

  • Factor IX activation by factor XIa proceeds without release of a free intermediate.

    abstract::Factor IX activation by factor XIa is thought to proceed through the singly-cleaved free intermediate, factor IX alpha. However, we observed no intermediate development during factor IX activation by factor XIa when using a low substrate to enzyme ratio (44:1 mol/mol). This result can be explained by one of two mechan...


    pub_type: 杂志文章


    authors: Wolberg AS,Morris DP,Stafford DW

    更新日期:1997-04-08 00:00:00

  • Structural domains of DNA mesojunctions.

    abstract::Holliday junctions are central intermediates in the process of genetic recombination. These DNA molecules contain four double helices that flank a central branch point, so that each of the four strands that constitute the junction is associated with two different helices. Previously, we have shown that such branched j...


    pub_type: 杂志文章


    authors: Wang H,Seeman NC

    更新日期:1995-01-24 00:00:00

  • Properties and regulation of the catalytic domain of Ira2p, a Saccharomyces cerevisiae GTPase-activating protein of Ras2p.

    abstract::This work describes the biochemical characterization of the catalytic domain of Ira2p, a Saccharomyces cerevisiae GTPase-activating protein (GAP) regulating the RAS gene products. A fragment of 383 residues (amino acids 1644-2026) was produced in Escherichia coli as glutathione S-transferase fusion protein (GST-Ira2p-...


    pub_type: 杂志文章


    authors: Parrini MC,Jacquet E,Bernardi A,Jacquet M,Parmeggiani A

    更新日期:1995-10-24 00:00:00

  • Catalytic and DNA binding properties of the ogg1 protein of Saccharomyces cerevisiae: comparison between the wild type and the K241R and K241Q active-site mutant proteins.

    abstract::The Ogg1 protein of Saccharomyces cerevisiae belongs to a family of DNA glycosylases and apurinic/apyrimidinic site (AP) lyases, the signature of which is the alpha-helix-hairpin-alpha-helix-Gly/Pro-Asp (HhH-GPD) active site motif together with a conserved catalytic lysine residue, to which we refer as the HhH-GPD/K f...


    pub_type: 杂志文章


    authors: Guibourt N,Castaing B,Van Der Kemp PA,Boiteux S

    更新日期:2000-02-22 00:00:00

  • Biochemical Characterization of the Two-Component Flavin-Dependent Monooxygenase Involved in Valanimycin Biosynthesis.

    abstract::The flavin reductase (FRED) and isobutylamine N-hydroxylase (IBAH) from Streptomyces viridifaciens constitute a two-component, flavin-dependent monooxygenase system that catalyzes the first step in valanimycin biosynthesis. FRED is an oxidoreductase that provides the reduced flavin to IBAH, which then catalyzes the hy...


    pub_type: 杂志文章


    authors: Li H,Forson B,Eckshtain-Levi M,Valentino H,Martín Del Campo JS,Tanner JJ,Sobrado P

    更新日期:2021-01-12 00:00:00

  • Nucleoside diphosphate kinase from bovine retina: purification, subcellular localization, molecular cloning, and three-dimensional structure.

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    pub_type: 杂志文章


    authors: Abdulaev NG,Karaschuk GN,Ladner JE,Kakuev DL,Yakhyaev AV,Tordova M,Gaidarov IO,Popov VI,Fujiwara JH,Chinchilla D,Eisenstein E,Gilliland GL,Ridge KD

    更新日期:1998-10-06 00:00:00

  • Exploration of the Effects of γ-Phosphate-Modified ATP Analogues on Histidine Kinase Autophosphorylation.

    abstract::While two-component systems (TCSs), composed of a sensor histidine kinase (HK) and a response regulator, are the main signaling pathways in bacteria, global TCS activity remains poorly described. Here, we report the kinetic parameters of the HK autophosphorylation reaction using previously uncharacterized γ-phosphate-...


    pub_type: 杂志文章


    authors: Chase OM,Espinasse A,Wilke KE,Carlson EE

    更新日期:2018-07-24 00:00:00

  • Insulin regulation of hepatic glycogen synthase and phosphorylase.

    abstract::The relative roles of insulin and glucose in the regulation of hepatic glycogen synthase and phosphorylase were studied in hepatocytes from fed rats. Elevation of extra-cellular glucose led to a rapid decrease in phosphorylase a activity followed by a slower increase in glycogen synthase I activity. A reciprocal and c...


    pub_type: 杂志文章


    authors: Witters LA,Avruch J

    更新日期:1978-02-07 00:00:00

  • Computational and in vitro analysis of destabilized DNA regions in the interferon gene cluster: potential of predicting functional gene domains.

    abstract::Recent evidence adds support to a traditional concept according to which the eukaryotic nucleus is organized into functional domains by scaffold or matrix attachment regions (S/MARs). These regions have previously been predicted to have a high potential for stress-induced duplex destabilization (SIDD). Here we report ...


    pub_type: 杂志文章


    authors: Goetze S,Gluch A,Benham C,Bode J

    更新日期:2003-01-14 00:00:00

  • Effect of insulin on ATP-citrate lyase phosphorylation: regulation of peptide A and peptide B phosphorylations.

    abstract::Insulin decreases multifunctional protein kinase (MFPK) activity in rat adipose tissue [Ramakrishna, S., & Benjamin, W. B. (1988) J. Biol. Chem. 263, 12677-12681]. Insulin also decreases the phosphorylation of peptide B but increases the phosphorylation of peptide A of ATP-citrate lyase (ATP-CL). The mechanism for thi...


    pub_type: 杂志文章


    authors: Ramakrishna S,Murthy KS,Benjamin WB

    更新日期:1989-01-24 00:00:00

  • Molecular interactions of nonpeptide agonists and antagonists with the melanocortin-4 receptor.

    abstract::The melanocortin-4 (MC4) receptor is a potential therapeutic target for obesity and cachexia, for which nonpeptide agonists and antagonists are being developed, respectively. The aim of this study was to identify molecular interactions between the MC4 receptor and nonpeptide ligands, and to compare the mechanism of bi...


    pub_type: 杂志文章


    authors: Fleck BA,Chen C,Yang W,Huntley R,Markison S,Nickolls SA,Foster AC,Hoare SR

    更新日期:2005-11-08 00:00:00

  • Structure and mechanism of an ADP-glucose phosphorylase from Arabidopsis thaliana.

    abstract::The X-ray crystal structure of the At5g18200.1 protein has been determined to a nominal resolution of 2.30 A. The structure has a histidine triad (HIT)-like fold containing two distinct HIT-like motifs. The sequence of At5g18200.1 indicates a distant family relationship to the Escherichia coli galactose-1-P uridylyltr...


    pub_type: 杂志文章


    authors: McCoy JG,Arabshahi A,Bitto E,Bingman CA,Ruzicka FJ,Frey PA,Phillips GN Jr

    更新日期:2006-03-14 00:00:00

  • Significance of hydrophobic S4-P4 interactions in subtilisin 309 from Bacillus lentus.

    abstract::The subtilisins have an extended substrate binding cleft comprising at least 8 subsites. Two pockets at the S1 and S4 sites are particularly conspicuous, and the interactions between substrate and these two pockets are very important for the substrate specificity. Phe residues have mutationally been introduced at one ...


    pub_type: 杂志文章


    authors: Bech LM,Sørensen SB,Breddam K

    更新日期:1993-03-23 00:00:00

  • Photochemical cleavage of DNA by nitrobenzamides linked to 9-aminoacridine.

    abstract::Nitrobenzamido ligands linked to the DNA intercalator 9-aminoacridine via poly(methylene) chains induce single-strand nicks in DNA upon irradiation with long-wavelength ultraviolet light (lambda greater than or equal to 300 nm). Optimal photocleavage activity was found for the reagent 9-[[6-(4-nitrobenzamido)hexyl]ami...


    pub_type: 杂志文章


    authors: Nielsen PE,Jeppesen C,Egholm M,Buchardt O

    更新日期:1988-08-23 00:00:00

  • The vitelline envelope of eggs from the giant keyhole limpet Megathura crenulata. II. Products formed by lysis with sperm enzymes and dithiothreitol.

    abstract::The egg vitelline envelope of the marine invertebrate, Megathura crenulata, was lyzed either by sperm lysins A, B, C or by dithiothreitol. In each case the lysis mixture consisted of two major fractions, I and II, that could be separated by hydroxylapatite chromatography and had different electrophoretic mobilities on...


    pub_type: 杂志文章


    authors: Heller E,Raftery MA

    更新日期:1976-03-23 00:00:00

  • Tyrosyl interactions in the folding and unfolding of bovine pancreatic ribonuclease A: a study of tyrosine-to-phenylalanine mutants.

    abstract::Three tyrosine-to-phenylalanine mutants of ribonuclease A (Y25F, Y92F, and Y97F) are investigated for their enzymatic activities, molecular stabilities, and unfolding/refolding kinetics. These mutants exhibit 80, 90, and 80%, respectively, of the catalytic activity of the wild-type enzyme. Thermal, Gdn.HCl, and pH tra...


    pub_type: 杂志文章


    authors: Juminaga D,Wedemeyer WJ,Garduño-Júarez R,McDonald MA,Scheraga HA

    更新日期:1997-08-19 00:00:00

  • Water structural changes in lumirhodopsin, metarhodopsin I, and metarhodopsin II upon photolysis of bovine rhodopsin: analysis by Fourier transform infrared spectroscopy.

    abstract::Difference Fourier transform infrared spectra of lumirhodopsin, metarhodopsin I, and metarhodopsin II versus rhodopsin were recorded with hydrated films of bovine rod outer segments at 200, 240, and 270 K. In the region between 3700 and 3450 cm-1, the O-H stretching vibrational bands of water were identified by H(2)18...


    pub_type: 杂志文章


    authors: Maeda A,Ohkita YJ,Sasaki J,Shichida Y,Yoshizawa T

    更新日期:1993-11-16 00:00:00

  • Isolation and characterization of bovine factor XII (Hageman factor).

    abstract::Factor XII was purified approximately 14 000-fold from bovine plasma by ammonium sulfate fractionation followed by heparin-agarose, DEAE-Sephadex, CM-cellulose, arginine-agarose, and benzamidine-agarose column chromatography. By this method, about 15 mg of protein was purified from 15 L of plasma with an overall yield...


    pub_type: 杂志文章


    authors: Fujikawa K,Walsh KA,Davie EW

    更新日期:1977-05-17 00:00:00

  • Dissection of events in the resistance to β-lactam antibiotics mediated by the protein BlaR1 from Staphylococcus aureus.

    abstract::A heterologous expression system was used to evaluate activation of BlaR1, a sensor/signal transducer protein of Staphylococcus aureus with a central role in resistance to β-lactam antibiotics. In the absence of other S. aureus proteins that might respond to antibiotics and participate in signal transduction events, w...


    pub_type: 杂志文章


    authors: Llarrull LI,Mobashery S

    更新日期:2012-06-12 00:00:00

  • Effect of solvent diffusion on the apomyoglobin-water interface.

    abstract::Few techniques can identify interactions between proteins and individual water molecules when the protein is in solution. The present work has sought to bridge the gap between the molecular level studies and the search for a physical property of the solution (bathing the proteins) that would regulate the protein hydra...


    pub_type: 杂志文章


    authors: Twist C,Royer C,Alpert B

    更新日期:2002-08-13 00:00:00

  • The swapping of terminal arms in ribonucleases: comparison of the solution structure of monomeric bovine seminal and pancreatic ribonucleases.

    abstract::Bovine seminal ribonuclease (BS-RNase), the only dimeric protein among the pancreatic-like ribonucleases, is endowed with special structural features and with biological functions beyond enzymatic activity. In solution, the protein exists as an equilibrium mixture of two forms, with or without exchange (or swapping) o...


    pub_type: 杂志文章


    authors: Avitabile F,Alfano C,Spadaccini R,Crescenzi O,D'Ursi AM,D'Alessio G,Tancredi T,Picone D

    更新日期:2003-07-29 00:00:00

  • Modulating Transmembrane α-Helix Interactions through pH-Sensitive Boundary Residues.

    abstract::Changes in pH can alter the structure and activity of proteins and may be used by the cell to control molecular function. This coupling can also be used in non-native applications through the design of pH-sensitive biomolecules. For example, the pH (low) insertion peptide (pHLIP) can spontaneously insert into a lipid ...


    pub_type: 杂志文章


    authors: Ng DP,Deber CM

    更新日期:2016-08-09 00:00:00