HIV-1 membrane fusion mechanism: structural studies of the interactions between biologically-active peptides from gp41.


:Two synthetic peptides corresponding to sequences in HIV-1LAI gp41, (aa558-595) and T20 (aa 643-678), are strong inhibitors of HIV-1 viral fusion, having EC50 values of 1 microgram/mL and 1 ng/mL, respectively. Previous work suggested that T21 forms a coiled-coil structure in PBS solution, while T20 is primarily nonhelical, and that the inhibitory action of these peptides occurs after the interaction between the viral gp120 protein and the cellular CD4 receptor [Wild, C.T., Shugars, D. C., Greenwell, T. K., McDanal, C. B., Matthews, T. J. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9770 and references therein]. The current study uses sedimentation equilibrium (SE), circular dichroism (CD), and viral-fusion assays to quantitatively investigate peptide structure and peptide-peptide interactions. SE analyses of T21 (1-100 microM) indicate that the peptide self associates via a monomer/dimer/tetramer equilibrium; in addition, T20 is monomeric in the range of 1-10 microM and exhibits a complicated monomer/tetramer equilibrium between 20 and 100 microM. Singular value decomposition analyses of the CD spectra of T21 and T20 indicate that the helical content of these peptides in PBS solution is 90% and 20%, respectively. A structural interaction between the two peptides is detected by CD at several concentration ratios of T20:T21. These experiments emphasize that T20 interacts specifically with the tetrameric form of T21. Truncated forms of T20 also exhibit structural interactions with T21 at varying concentration ratios. The ability of T20 and the truncated peptides to interact structurally with tetrameric T21 correlates with antiviral activity. Implications of these findings are discussed in terms of proposed mechanisms of membrane fusion inhibition and the structural changes which occur in gp41 during membrane fusion.






Lawless MK,Barney S,Guthrie KI,Bucy TB,Petteway SR Jr,Merutka G




Has Abstract


1996-10-22 00:00:00














  • Effects of base composition on the negative cooperativity and binding mode transitions of Escherichia coli SSB-single-stranded DNA complexes.

    abstract::We have examined the ability of the Escherichia coli single-stranded DNA binding protein (SSB) tetramer to form its different binding modes on poly(dC), poly(U), and poly(A) over a range of NaCl and NaF concentrations for comparison with previous studies with poly(dT). In reverse titrations with poly(U) and poly(A) at...


    pub_type: 杂志文章


    authors: Lohman TM,Bujalowski W

    更新日期:1994-05-24 00:00:00

  • Kinetic, crystallographic, and mechanistic characterization of TomN: elucidation of a function for a 4-oxalocrotonate tautomerase homologue in the tomaymycin biosynthetic pathway.

    abstract::The biosynthesis of the C ring of the antitumor antibiotic agent, tomaymycin, is proposed to proceed through five enzyme-catalyzed steps from l-tyrosine. The genes encoding these enzymes have recently been cloned and their functions tentatively assigned, but there is limited biochemical evidence supporting the assignm...


    pub_type: 杂志文章


    authors: Burks EA,Yan W,Johnson WH Jr,Li W,Schroeder GK,Min C,Gerratana B,Zhang Y,Whitman CP

    更新日期:2011-09-06 00:00:00

  • Redesign of cosubstrate specificity and identification of important residues for substrate binding to hChAT.

    abstract::In eukaryotes, choline acetyltransferase (ChAT) catalyzes the reversible formation of the neurotransmitter acetylcholine from choline and acetyl-CoA. ChAT belongs to a family of CoA-dependent enzymes that also includes the carnitine acyltransferases CrAT, CrOT, and CPTs. In contrast to CrOT and CPTs that are very acti...


    pub_type: 杂志文章


    authors: Green KD,Porter VR,Zhang Y,Garneau-Tsodikova S

    更新日期:2010-07-27 00:00:00

  • Binding of proteins to specific target sites in membranes measured by total internal reflection fluorescence microscopy.

    abstract::A new quantitative technique for measuring the binding of proteins to membranes is described. The method is based on a combination of total internal reflection fluorescence microscopy and the preparation of supported planar bilayers. Specific and reversible binding of a fluorescence-labeled monoclonal antibody to lipi...


    pub_type: 杂志文章


    authors: Kalb E,Engel J,Tamm LK

    更新日期:1990-02-13 00:00:00

  • Short sequences of non-proline residues can adopt the polyproline II helical conformation.

    abstract::The left-handed polyproline II (P(II)) helix is a structure that has been given a great deal of attention lately because of its role in a wide variety of physiologically important processes and potential significance in protein unfolded states. Recent work by several authors has shown that residues besides proline can...


    pub_type: 杂志文章


    authors: Chellgren BW,Creamer TP

    更新日期:2004-05-18 00:00:00

  • Resonance raman analysis of chromophore structure in the lumi-R photoproduct of phytochrome.

    abstract::Resonance Raman vibrational spectra of the Pr, lumi-R, and Pfr forms of phytochrome have been obtained using low-temperature trapping and room temperature flow techniques in conjunction with shifted-excitation Raman difference spectroscopy (SERDS). The Pr to lumi-R photoconversion exhibits a thermal barrier and is com...


    pub_type: 杂志文章


    authors: Andel F 3rd,Lagarias JC,Mathies RA

    更新日期:1996-12-17 00:00:00

  • Affinity cleavage at the metal-binding site of phosphoenolpyruvate carboxykinase.

    abstract::Chicken liver phosphoenolpyruvate carboxykinase (PEPCK) was rapidly inactivated by micromolar concentrations of ferrous sulfate in the presence of ascorbate at pH 7.4. Omitting ascorbate or replacing the Fe2+ with Mn2+ or Mg2+ gives no inactivation. Mn2+, Mg2+, or Co2+ at 100-fold molar excess over Fe2+ offered comple...


    pub_type: 杂志文章


    authors: Hlavaty JJ,Nowak T

    更新日期:1997-12-09 00:00:00

  • Active site specific cadmium(II)-substituted horse liver alcohol dehydrogenase: crystal structures of the free enzyme, its binary complex with NADH, and the ternary complex with NADH and bound p-bromobenzyl alcohol.

    abstract::Three crystal structures have been determined of active site specific substituted Cd(II) horse liver alcohol dehydrogenase and its complexes. Intensities were collected for the free, orthorhombic enzyme to 2.4-A resolution and for a triclinic binary complex with NADH to 2.7-A resolution. A ternary complex was crystall...


    pub_type: 杂志文章


    authors: Schneider G,Cedergren-Zeppezauer E,Knight S,Eklund H,Zeppezauer M

    更新日期:1985-12-03 00:00:00

  • Phospholipid-binding properties of bovine factor V and factor Va.

    abstract::Factor V and factor Va binding to single bilayer phospholipid vesicles was investigated by light-scattering intensity measurements. This technique allows the measurement of free and phospholipid-bound protein concentrations from which equilibrium constants can be obtained. As controls, the Ca2+-dependent phospholipid ...


    pub_type: 杂志文章


    authors: Bloom JW,Nesheim ME,Mann KG

    更新日期:1979-10-02 00:00:00

  • Characterization of synthetic human granulocyte chemotactic protein 2: usage of chemokine receptors CXCR1 and CXCR2 and in vivo inflammatory properties.

    abstract::Human granulocyte chemotactic protein 2 (GCP-2) has originally been isolated from cytokine-stimulated osteosarcoma cells as a chemokine coproduced in minute amounts together with interleukin 8. Human GCP-2 (75 residues) was synthesized on a 0.25-mmol scale using Fmoc chemistry. After disulfide bridge formation and pur...


    pub_type: 杂志文章


    authors: Wuyts A,Van Osselaer N,Haelens A,Samson I,Herdewijn P,Ben-Baruch A,Oppenheim JJ,Proost P,Van Damme J

    更新日期:1997-03-04 00:00:00

  • Jeltraxin, a frog egg jelly glycoprotein, has calcium-dependent lectin properties and is related to human serum pentraxins CRP and SAP.

    abstract::The egg jelly that encapsulates amphibian eggs is essential for fertilization, but its molecular composition and roles remain largely unknown. We identified a calcium-dependent lectin from the pentraxin superfamily in the egg jelly coat from the South American burrowing frog, Lepidobatrachus laevis. This lectin, jeltr...


    pub_type: 杂志文章


    authors: Peavy TR,Hernandez C,Carroll EJ Jr

    更新日期:2003-11-11 00:00:00

  • Nucleosome Histone Tail Conformation and Dynamics: Impacts of Lysine Acetylation and a Nearby Minor Groove Benzo[a]pyrene-Derived Lesion.

    abstract::Histone tails in nucleosomes play critical roles in regulation of many biological processes, including chromatin compaction, transcription, and DNA repair. Moreover, post-translational modifications, notably lysine acetylation, are crucial to these functions. While the tails have been intensively studied, how the stru...


    pub_type: 杂志文章


    authors: Fu I,Cai Y,Geacintov NE,Zhang Y,Broyde S

    更新日期:2017-04-11 00:00:00

  • Effect of sequence on the conformation of DNA holliday junctions.

    abstract::Structures of the DNA sequences d(CCGGCGCCGG) and d(CCAGTACbr(5)UGG) are presented here as four-way Holliday junctions in their compact stacked-X forms, with antiparallel alignment of the DNA strands. Thus, the ACC-trinucleotide motif, previously identified as important for stabilizing the junction, is now extended to...


    pub_type: 杂志文章


    authors: Hays FA,Vargason JM,Ho PS

    更新日期:2003-08-19 00:00:00

  • Atomic force microscopy imaging reveals the domain structure of polycystin-1.

    abstract::Mutation of polycystin-1 (PC1) is the major cause of autosomal dominant polycystic kidney disease. PC1 has a predicted molecular mass of ~460 kDa comprising a long multidomain extracellular N-terminal region, 11 transmembrane regions, and a short C-terminal region. Because of its size, PC1 has proven difficult to hand...


    pub_type: 杂志文章


    authors: Oatley P,Stewart AP,Sandford R,Edwardson JM

    更新日期:2012-04-03 00:00:00

  • Mechanisms by which human DNA primase chooses to polymerize a nucleoside triphosphate.

    abstract::Human DNA primase synthesizes short RNA primers that DNA polymerase alpha then elongates during the initiation of all new DNA strands. Even though primase misincorporates NTPs at a relatively high frequency, this likely does not impact the final DNA product since the RNA primer is replaced with DNA. We used an extensi...


    pub_type: 杂志文章


    authors: Urban M,Joubert N,Purse BW,Hocek M,Kuchta RD

    更新日期:2010-02-02 00:00:00

  • Side-chain interactions in the folding pathway of a Fyn SH3 domain mutant studied by relaxation dispersion NMR spectroscopy.

    abstract::A major challenge to the study of protein folding is the fact that intermediate states along the reaction pathway are generally unstable and thus difficult to observe. Recently developed NMR relaxation dispersion experiments present an avenue to accessing such states, providing kinetic, thermodynamic, and structural i...


    pub_type: 杂志文章


    authors: Mittermaier A,Korzhnev DM,Kay LE

    更新日期:2005-11-29 00:00:00

  • Characterization of the internal motions of Escherichia coli ribonuclease HI by a combination of 15N-NMR relaxation analysis and molecular dynamics simulation: examination of dynamic models.

    abstract::The backbone dynamics of Escherichia coli ribonuclease HI (RNase HI) in the picosecond to nanosecond time scale were characterized by a combination of measurements of 15N-NMR relaxation (T1, T2, and NOE), analyzed by a model-free approach, and molecular dynamics (MD) simulation in water. The MD simulations in water we...


    pub_type: 杂志文章


    authors: Yamasaki K,Saito M,Oobatake M,Kanaya S

    更新日期:1995-05-23 00:00:00

  • Influence of the calcium-induced gel phase on the behavior of small molecules in phosphatidylserine and phosphatidylserine-phosphatidylcholine multilamellar vesicles.

    abstract::The behavior of fluorescent and spin-label probes is examined in several fluid and gel phospholipid phases, with particular focus on the Ca2+-induced gel phase in phosphatidylserine (PS). These probes have behavior characteristic of the type of probe and of the type of lipid environment. Anthroyloxy- and doxyl-labeled...


    pub_type: 杂志文章


    authors: Florine KI,Feigenson GW

    更新日期:1987-03-24 00:00:00

  • Topological disposition of lysine 943 in native Na+/K(+)-transporting ATPase.

    abstract::Because of the conflicting conclusions that have been reached regarding the location of the two putative membrane-spanning segments from cysteine 911 through isoleucine 929 and from isoleucine 946 through cysteine 964 in the alpha subunit of native ovine Na+/K(+)-transporting ATPase, the disposition of lysine 943 with...


    pub_type: 杂志文章


    authors: Anderberg SJ

    更新日期:1995-07-25 00:00:00

  • Elsamicin A can convert the Z-form of poly[d(G-C)] and poly[(G-m5C)] back to B-form DNA.

    abstract::The interaction of poly[(G-C)] and poly[d(G-m5C)] with the antitumor antibiotic elsamicin A, which binds to alternating guanine + cytosine tracts in DNA, has been studied under the B and Z conformations. Both the rate and the extent of the B-to-Z transition are diminished by the antibiotic, as inferred by spectroscopi...


    pub_type: 杂志文章


    authors: Jiménez-García E,Portugal J

    更新日期:1992-11-24 00:00:00

  • Stimulation of transcript elongation requires both the zinc finger and RNA polymerase II binding domains of human TFIIS.

    abstract::The eukaryotic transcriptional factor TFIIS enhances transcript elongation by RNA polymerase II. Here we describe two functional domains in the 280 amino acid human TFIIS protein: residues within positions 100-230 are required for binding to polymerase, and residues 230-280, which form a zinc finger, are required in c...


    pub_type: 杂志文章


    authors: Agarwal K,Baek KH,Jeon CJ,Miyamoto K,Ueno A,Yoon HS

    更新日期:1991-08-06 00:00:00

  • Effects of cholesterol on surface activity and surface topography of spread surfactant films.

    abstract::Pulmonary surfactant forms a monolayer of lipids and proteins at the alveolar air/liquid interface. Although cholesterol is a natural component of surfactant, its function in surface dynamics is unclear. To further elucidate the role of cholesterol in surfactant, we used a captive bubble surfactometer (CBS) to measure...


    pub_type: 杂志文章


    authors: Diemel RV,Snel MM,Van Golde LM,Putz G,Haagsman HP,Batenburg JJ

    更新日期:2002-12-17 00:00:00

  • Mechanism of regulation of cardiac actin-myosin subfragment 1 by troponin-tropomyosin.

    abstract::The effect of Ca2+ on the interaction of bovine cardiac myosin subfragment 1 (S-1) with actin regulated by cardiac troponin-tropomyosin was evaluated. The ratios of actin to troponin and to tropomyosin were adjusted to optimize the Ca2+-dependent regulation of the steady-state actin-activated magnesium adenosinetripho...


    pub_type: 杂志文章


    authors: Tobacman LS,Adelstein RS

    更新日期:1986-02-25 00:00:00

  • Nucleation of actin polymerization by villin and elongation at subcritical monomer concentration.

    abstract::We have obtained a quantitative description of villin-nucleated actin polymerization in physiological salt by determining the concentrations of free villin (V), villin-actin monomer (VA), villin-actin dimer (VA2), and villin-actin oligomer (VAn). Over a range of actin-villin ratios from 0.1 to 20 we determined the con...


    pub_type: 杂志文章


    authors: Weber A,Northrop J,Bishop MF,Ferrone FA,Mooseker MS

    更新日期:1987-05-05 00:00:00

  • Epsilon amino caproic acid inhibits streptokinase-plasminogen activator complex formation and substrate binding through kringle-dependent mechanisms.

    abstract::Lysine side chains induce conformational changes in plasminogen (Pg) that regulate the process of fibrinolysis or blood clot dissolution. A lysine side-chain mimic, epsilon amino caproic acid (EACA), enhances the activation of Pg by urinary-type and tissue-type Pg activators but inhibits Pg activation induced by strep...


    pub_type: 杂志文章


    authors: Lin LF,Houng A,Reed GL

    更新日期:2000-04-25 00:00:00

  • Hydrophobic core fluidity of homologous protein domains: relation of side-chain dynamics to core composition and packing.

    abstract::The side-chain dynamics of methyl groups in two structurally related proteins from the fibronectin type III (fnIII) superfamily, the third fnIII domain from human tenascin (TNfn3) and the tenth fnIII domain from human fibronectin (FNfn10), have been studied by NMR spectroscopy. Side-chain order parameters reveal that ...


    pub_type: 杂志文章


    authors: Best RB,Rutherford TJ,Freund SM,Clarke J

    更新日期:2004-02-10 00:00:00

  • Hemoglobin of the Antarctic fishes Trematomus bernacchii and Trematomus newnesi: structural basis for the increased stability of the liganded tetramer relative to human hemoglobin.

    abstract::Hemoglobins extracted from fishes that live in temperate waters show little or no dissociation even in the liganded form, unlike human hemoglobin (HbA). To establish whether cold adaptation influences the tendency to dissociate, the dimer-tetramer association constants (L(2,4)) of the carbonmonoxy derivatives of repre...


    pub_type: 杂志文章


    authors: Giangiacomo L,D'Avino R,di Prisco G,Chiancone E

    更新日期:2001-03-13 00:00:00

  • Immunoaffinity purification and properties of a high molecular weight calf thymus DNA alpha-polymerase.

    abstract::A rapid, three-step purification of DNA alpha-polymerase from calf thymus is described. The key feature is immunoaffinity chromatography using a column of immobilized monoclonal immunoglobulin G (IgG) developed against human KB cell alpha-polymerase. This step is followed by preparative sucrose gradient sedimentation....


    pub_type: 杂志文章


    authors: Wahl AF,Kowalski SP,Harwell LW,Lord EM,Bambara RA

    更新日期:1984-04-24 00:00:00

  • Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines.

    abstract::Quinone oxidoreductase 2 (QR2) purified from human red blood cells was recently shown to be a potential target of the quinoline antimalarial compounds [Graves et al., (2002) Mol. Pharmacol. 62, 1364]. QR2 catalyzes the two-electron reduction of menadione via the oxidation of N-alkylated or N-ribosylated nicotinamides....


    pub_type: 杂志文章


    authors: Kwiek JJ,Haystead TA,Rudolph J

    更新日期:2004-04-20 00:00:00

  • Circular dichroism and fluorescence studies of homogeneous antibodies to type III pneumococcal polysaccharide.

    abstract::The near-ultraviolet circular dichroism (CD) of three homogeneous anti-type III pneumococcal antibodies in the absence and the presence of the specific hexasaccharide ligand was studied. In addition recombinations and hybridizations of H and L chains derived from two of these antibodies were carried out and the CD spe...


    pub_type: 杂志文章


    authors: Jaton JC,Huser H,Blatt Y,Pecht I

    更新日期:1975-12-02 00:00:00