Misfolding of the cystic fibrosis transmembrane conductance regulator and disease.


:Understanding the structural basis for defects in protein function that underlie protein-based genetic diseases is the fundamental requirement for development of therapies. This situation is epitomized by the cystic fibrosis transmembrane conductance regulator (CFTR)-the gene product known to be defective in CF patients-that appears particularly susceptible to misfolding when its biogenesis is hampered by mutations at critical loci. While the primary CF-related defect in CFTR has been localized to deletion of nucleotide binding fold (NBD1) residue Phe508, an increasing number of mutations (now ca. 1,500) are being associated with CF disease of varying severity. Hundreds of these mutations occur in the CFTR transmembrane domain, the site of the protein's chloride channel. This report summarizes our current knowledge on how mutation-dependent misfolding of the CFTR protein is recognized on the cellular level; how specific types of mutations can contribute to the misfolding process; and describes experimental approaches to detecting and elucidating the structural consequences of CF-phenotypic mutations.






Cheung JC,Deber CM




Has Abstract


2008-02-12 00:00:00












  • COUP-TF plays a dual role in the regulation of the ovalbumin gene.

    abstract::The ovalbumin (Ov) gene contains a number of regulatory elements that control its transcriptional activity and restrict expression to avian oviduct. One major regulatory region, the steroid-dependent regulatory element (SDRE), is required for induction by estrogen and corticosterone. Another region, the negative regul...


    pub_type: 杂志文章


    authors: Park HM,Haecker SE,Hagen SG,Sanders MM

    更新日期:2000-07-25 00:00:00

  • Cadmium-113 NMR studies of the DNA binding domain of the mammalian glucocorticoid receptor.

    abstract::The DNA binding domain of the mammalian glucocorticoid hormone receptor (GR) contains nine highly conserved cysteine residues, a conservation shared by the superfamily of steroid and thyroid hormone receptors. A fragment [150 amino acids (AA) in length] consisting of GR residues 407-556, containing within it the entir...


    pub_type: 杂志文章


    authors: Pan T,Freedman LP,Coleman JE

    更新日期:1990-10-02 00:00:00

  • The room temperature reaction of carbon monoxide and oxygen with the cytochrome bd quinol oxidase from Escherichia coli.

    abstract::When grown under O2-limited conditions, Escherichia coli expresses a cytochrome bd quinol oxidase that has an unusually high affinity for O2. We have studied the reaction of cytochrome bd with CO and O2 by rapid-reaction spectrophotometry. The reduced enzyme forms a photosensitive ferrocytochrome d-CO complex, and fol...


    pub_type: 杂志文章


    authors: Hill BC,Hill JJ,Gennis RB

    更新日期:1994-12-20 00:00:00

  • Self-association of linker histone H5 and of its globular domain: evidence for specific self-contacts.

    abstract::The ability of avian-specific linker histone H5, and the globular domains of H5 (GH5) and H1(0) (GH1(0), to self-associate either free in solution or when bound to DNA was investigated. All three proteins underwent a salt-dependent increase in turbidity that may be indicative of nonspecific interactions. Dithiobis(suc...


    pub_type: 杂志文章


    authors: Carter GJ,van Holde K

    更新日期:1998-09-08 00:00:00

  • Cysteine auxotrophy of human leukemic lymphoblasts is associated with decreased amounts of intracellular cystathionase protein.

    abstract::A series of human lymphoblastoid cell lines derived from nonleukemic donors are known to be cysteine prototrophs (cys+), while several lymphoblastoid lines derived from leukemic donors are cysteine auxotrophs (cys-). We have tested representative cell lines of each type for their content of cystathionase enzyme activi...


    pub_type: 杂志文章


    authors: Glode LM,Kriegler MP,Livingston DM

    更新日期:1981-03-03 00:00:00

  • Sequence effects on the conformational properties of the amyloid beta (1-28) peptide: testing a proposed mechanism for the alpha-->beta transition.

    abstract::Molecular dynamics simulations have been used to successfully reproduce the observed pH-dependent conformational properties of the amyloid beta(1-28) peptide [Kirshenbaum and Daggett (1995) Biochemistry, 34, 7629-7639]. On the basis of these simulations a mechanism was proposed for the unfolding of the N-terminal port...


    pub_type: 杂志文章


    authors: Kirshenbaum K,Daggett V

    更新日期:1995-06-13 00:00:00

  • Structural and thermodynamic basis of affinity in anti-dinitrophenyl antibody.

    abstract::The thermodynamic quantities of the anti-dinitrophenyl antibody-hapten interaction are reported for rabbit, goat, and guinea pig antibodies. Rabbit and goat antibodies had similar exothermic enthalpy changes for their reaction with 2,4-dinitrophenyl-L-lysine (-13.9 and -14.8 kcal/mol, respectively). The enthalpy chang...


    pub_type: 杂志文章


    authors: Halsey JF,Cebra JJ,Biltonen RL

    更新日期:1975-11-18 00:00:00

  • Quinone (Q(B)) binding site and protein stuctural changes in photosynthetic reaction center mutants at Pro-L209 revealed by vibrational spectroscopy.

    abstract::The effect of substituting Pro-L209 with Tyr, Phe, Glu, and Thr in photosynthetic reaction centers (RCs) from Rhodobacter sphaeroides was investigated by monitoring the light-induced FTIR absorption changes associated with the photoreduction of the secondary quinone Q(B). Pro-L209 is close to a chain of ordered water ...


    pub_type: 杂志文章


    authors: Nabedryk E,Breton J,Sebban P,Baciou L

    更新日期:2003-05-20 00:00:00

  • Recognition of Dictyostelium discoideum lysosomal enzymes is conferred by the amino-terminal carbohydrate binding site of the insulin-like growth factor II/mannose 6-phosphate receptor.

    abstract::The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/MPR) is a type I glycoprotein that mediates both the intracellular sorting of lysosomal enzymes bearing mannose 6-phosphate (Man-6-P) residues to the lysosome and the bioavailability of IGF-II. The extracytoplasmic region of the IGF-II/MPR contains...


    pub_type: 杂志文章


    authors: Marron-Terada PG,Hancock MK,Haskins DJ,Dahms NM

    更新日期:2000-03-07 00:00:00

  • Induction by torsional stress of an altered DNA conformation 5' upstream of the gene for a high mobility group protein from trout and specific binding to flanking sequences by the gene product HMG-T.

    abstract::We have used enzymic and chemical probes to search for altered DNA conformations in the 5' flanking region of the gene for a high mobility group protein (HMG-T) from trout. This search was conducted in order to identify potential genetic elements that might be involved in the transcriptional control of the HMG-T gene....


    pub_type: 杂志文章


    authors: Wright JM,Dixon GH

    更新日期:1988-01-26 00:00:00

  • Molecular organization in striated domains induced by transmembrane alpha-helical peptides in dipalmitoyl phosphatidylcholine bilayers.

    abstract::Transmembrane (TM) alpha-helical peptides with neutral flanking residues such as tryptophan form highly ordered striated domains when incorporated in gel-state 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers and inspected by atomic force microscopy (AFM) (1). In this study, we analyze the molecular organiz...


    pub_type: 杂志文章


    authors: Sparr E,Ganchev DN,Snel MM,Ridder AN,Kroon-Batenburg LM,Chupin V,Rijkers DT,Killian JA,de Kruijff B

    更新日期:2005-01-11 00:00:00

  • Competition between Fibrillation and Induction of Vesicle Fusion for the Membrane-Associated 40-Residue β-Amyloid Peptides.

    abstract::Disruption of the cell membrane by the β-amyloid (Aβ) peptides has been considered as a main mechanism of Alzheimer's disease. The peptide-to-lipid molar ratio (P:L) varies over a broad range biologically. We report here that two of the previously observed Aβ evolution pathways, fibrillation and induction of vesicle f...


    pub_type: 杂志文章


    authors: Akinlolu RD,Nam M,Qiang W

    更新日期:2015-06-09 00:00:00

  • Membrane interactions of mutated forms of the influenza fusion peptide.

    abstract::We have studied a group of fusion peptides of influenza hemagglutinin in which the N-terminal amino acid, Gly (found in the wild-type peptide), has been systematically substituted with Ala, Ser, Val, or Glu. The activity of the intact hemagglutinin protein with these same substitutions has already been reported. As a ...


    pub_type: 杂志文章


    authors: Epand RM,Epand RF,Martin I,Ruysschaert JM

    更新日期:2001-07-31 00:00:00

  • Electrostatic optimization of the conformational energy landscape in a metamorphic protein.

    abstract::The equilibrium unfolding reaction of Ltn, a metamorphic C-class chemokine, was monitored by tryptophan fluorescence to determine unfolding free energies. Measurements revealed that addition of 150 mM NaCl stabilized the Ltn chemokine fold by approximately 1 kcal/mol. Specific mutations involving Arg23 and Arg43 also ...


    pub_type: 杂志文章


    authors: Tyler RC,Wieting JC,Peterson FC,Volkman BF

    更新日期:2012-11-13 00:00:00

  • Electron exchange between Fe(II)-horse spleen ferritin and Co(III)/Mn(III) reconstituted horse spleen and Azotobacter vinelandii ferritins.

    abstract::Azotobacter vinelandii bacterioferritin (AvBF) containing 800-1500 Co or Mn atoms as Co(III) and Mn(III) oxyhydroxide cores (Co-AvBF, Mn-AvBF) was synthesized by the same procedure used previously for horse spleen ferritin (HoSF). The kinetics of reduction of Co-AvBF and Mn-AvBF by ascorbic acid are first-order in eac...


    pub_type: 杂志文章


    authors: Zhang B,Harb JN,Davis RC,Choi S,Kim JW,Miller T,Chu SH,Watt GD

    更新日期:2006-05-09 00:00:00

  • Cytochrome c peroxidase mutant active site structures probed by resonance Raman and infrared signatures of the CO adducts.

    abstract::Vibrational frequencies associated with FeC and CO stretching and FeCO bending modes have been determined via resonance Raman (RR) and infrared (IR) spectroscopy for cytochrome c peroxidase (CCP) mutants prepared by site-directed mutagenesis. These include the bacterial "wild type", CCP(MI), and mutations involving gr...


    pub_type: 杂志文章


    authors: Smulevich G,Mauro JM,Fishel LA,English AM,Kraut J,Spiro TG

    更新日期:1988-07-26 00:00:00

  • Independent heterologous fibrillation of insulin and its B-chain peptide.

    abstract::Insulin is very prone to form amyloid fibrils under slightly destabilizing conditions, and the B-chain region plays a critical role in the fibrillation. We show here that the isolated B-chain peptide of bovine insulin also forms fibrils at both acidic and neutral pH. When a mixture of insulin and the B-chain peptide w...


    pub_type: 杂志文章


    authors: Hong DP,Fink AL

    更新日期:2005-12-20 00:00:00

  • Tryptophan 500 and arginine 707 define product and substrate active site binding in soybean lipoxygenase-1.

    abstract::There is much debate whether the fatty acid substrate of lipoxygenase binds "carboxylate-end first" or "methyl-end first" in the active site of soybean lipoxygenase-1 (sLO-1). To address this issue, we investigated the sLO-1 mutants Trp500Leu, Trp500Phe, Lys260Leu, and Arg707Leu with steady-state and stopped-flow kine...


    pub_type: 杂志文章


    authors: Ruddat VC,Mogul R,Chorny I,Chen C,Perrin N,Whitman S,Kenyon V,Jacobson MP,Bernasconi CF,Holman TR

    更新日期:2004-10-19 00:00:00

  • Nucleotide specificity of stringent factor and the synthesis of analogs of guanosine 5'-diphosphate 3'-diphosphate and guanosine 5'-triphosphate 3'-diphosphate.

    abstract::The ribosome-dependent stringent factor reaction was found to be nonspecific with regard to the number of phosphate groups linked to the 5' position of guanosine nucleotides. Both GMP and guanosine 5'-tetraphosphate could accept a pyrophosphoryl group from ATP although at a much lower rate than GDP or GTP. Guanosine 5...


    pub_type: 杂志文章


    authors: Sy J

    更新日期:1975-03-11 00:00:00

  • Conversion of cytochrome f to a soluble form in vivo in Chlamydomonas reinhardtii.

    abstract::We introduced a stop codon in place of the ATT codon encoding Ile283 (numbered from the Met initiation codon) in the petA gene from Chlamydomonas reinhardtii. The resulting protein was expected to be truncated on its carboxy-terminus end, lacking the last 35 amino acids. This region of the polypeptide sequence encompa...


    pub_type: 杂志文章


    authors: Kuras R,Wollman FA,Joliot P

    更新日期:1995-06-06 00:00:00

  • Enhancement of Agkistrodon piscivorus piscivorus venom phospholipase A2 activity toward phosphatidylcholine vesicles by lysolecithin and palmitic acid: studies with fluorescent probes of membrane structure.

    abstract::The activity of phospholipase A2 from snake venom to hydrolyze bilayers of phosphatidylcholines is greatly enhanced by the presence of the hydrolysis products, lysolecithin and fatty acid, in the bilayer. The fluorescence of several probes of membrane structure was used to monitor changes in bilayer physical propertie...


    pub_type: 杂志文章


    authors: Sheffield MJ,Baker BL,Li D,Owen NL,Baker ML,Bell JD

    更新日期:1995-06-20 00:00:00

  • Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain.

    abstract::Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor belonging to the ParaHox family. Pdx1 plays an essential role in pancreatic endocrine and exocrine cell development and maintenance of adult islet beta-cell function. Mutations in the human pdx1 gene are linked to an early onset form of no...


    pub_type: 杂志文章


    authors: Longo A,Guanga GP,Rose RB

    更新日期:2007-03-20 00:00:00

  • Analysis of the kinetics of ovine follitropin agonist-antagonist interactions with pig ovarian membranes.

    abstract::The binding of 125I-labeled ovine follitropin (oFSH) and 125I-labeled deglycosylated ovine follitropin (DG-oFSH) to porcine granulosa cell membranes was studied at equilibrium and nonequilibrium binding conditions and statistically analyzed. Saturation and competition binding experiments revealed homogeneity in the po...


    pub_type: 杂志文章


    authors: Sebok K,De Lean A,Sairam MR

    更新日期:1987-06-16 00:00:00

  • The active-site histidine-10 of enterococcal NADH peroxidase is not essential for catalytic activity.

    abstract::In order to test the proposal [Stehle, T., Claiborne, A., & Schulz, G. E. (1993) Eur. J. Biochem. 211, 221-226] that the active-site His10 of NADH peroxidase functions as an essential acid-base catalyst, we have analyzed mutants in which this residue has been replaced by Gln or Ala. The k(cat) values for both H10Q and...


    pub_type: 杂志文章


    authors: Crane EJ 3rd,Parsonage D,Claiborne A

    更新日期:1996-02-20 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

  • Reaction of neuronal nitric-oxide synthase with 2,6-dichloroindolphenol and cytochrome c3+: influence of the electron acceptor and binding of Ca2+-activated calmodulin on the kinetic mechanism.

    abstract::Binding of Ca(2+)-activated calmodulin (Ca(2+)-CaM) to neuronal nitric-oxide synthase (nNOS) increases the rate of 2,6-dichloroindolphenol (DCIP) reduction 2-3-fold and that of cytochrome c(3+) 10-20-fold. Parallel initial velocity patterns indicated that both substrates were reduced via two-half reactions in a ping-p...


    pub_type: 杂志文章


    authors: Wolthers KR,Schimerlik MI

    更新日期:2001-04-17 00:00:00

  • Detergents stabilize the conformation of phosphodiesterase 6.

    abstract::Membrane-bound phosphodiesterase 6 (PDE6) plays an important role in visual signal transduction by regulating cGMP levels in rod photoreceptor cells. Our understanding of PDE6 catalysis and structure suffers from inadequate characterization of the α and β subunit catalytic core, interactions of the core with two intri...


    pub_type: 杂志文章


    authors: Baker BY,Palczewski K

    更新日期:2011-11-08 00:00:00

  • Elucidation of the chemical nature of the steady-state intermediates in the mechanism of carboxypeptidase A.

    abstract::Cryospectrokinetic studies of zinc and cobalt carboxypeptidase A disclosed two intermediates in the hydrolysis of both peptides and depsipeptides and furnished all the rate and equilibrium constants for the reaction scheme E + S in equilibrium ES1 in equilibrium ES2---E + P [Auld, D. S., Galdes, A., Geoghegan, K. F., ...


    pub_type: 杂志文章


    authors: Galdes A,Auld DS,Vallee BL

    更新日期:1986-02-11 00:00:00

  • Tetrahydrobiopterin-free neuronal nitric oxide synthase: evidence for two identical highly anticooperative pteridine binding sites.

    abstract::The properties of neuronal nitric oxide synthase containing one tetrahydrobiopterin (BH4) per dimer [nNOS(BH4+)] were compared to those of the BH4-free enzyme [nNOS(BH4-)]. The stimulation by BH4 of the formation of L-citrulline at the expense of H2O2 production unambiguously demonstrated that BH4 is essential in coup...


    pub_type: 杂志文章


    authors: Gorren AC,List BM,Schrammel A,Pitters E,Hemmens B,Werner ER,Schmidt K,Mayer B

    更新日期:1996-12-24 00:00:00

  • Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis.

    abstract::During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast AD...


    pub_type: 杂志文章


    authors: Plapp BV,Savarimuthu BR,Ferraro DJ,Rubach JK,Brown EN,Ramaswamy S

    更新日期:2017-07-18 00:00:00